Herbal Highlight

Mugwort is a common weed in Europe and Great Britain which resulted in it becoming a popular flavouring agent for homebrews long before hops was the preferred plant used in beers. As Maud Grieve said, in A Modern Herbal (1931), “mugwort abounds on hedgebanks and waysides in most parts of England.” Grieve said mugwort’s common name is derived from its reputation as a brewing herb - a mug full of wort (medicinal herb). However, she also suggests that the name may stem not from mug, the drinking vessel, but from moughte (a moth or maggot) because, from the days of Dioscorides (a Greek physician who wrote De Materia Medica in the first century AD), the plant has been regarded as useful in repelling attacks by moths and other insects, not unlike its close ally wormwood (Artemisia absinthium).

Mugwort’s botanical name hints at its affinity for menstrual and reproductive health. Artemis is the Greek goddess of childbirth and the moon (the word menstruation comes from the Latin and Greek words for month and moon), and mugwort has been used as a supportive herb for uterine and reproductive health across many herbal traditions. It may be used as an emmenagogue and to aid normal menstrual flow. It can also facilitate childbirth by regulating and strengthening contractions and helping bring away the afterbirth. 

As a warming bitter, mugwort can stimulate circulation, digestion and menses while simultaneously easing muscle cramping and stagnation. It supports digestion through bitter stimulation while also possessing carminative properties. As a result it has been used traditionally for treating gynaecological ailments and gastrointestinal diseases resulting from cold including delayed menses, stomach pain, diarrhoea, flatulence and intestinal colic.

References

Grieve M. A Modern Herbal. Penguin:London; 1980. p. 556

McIntyre A. The Complete Women’s Herbal. London: Gaia Books Limited, 1994. p. 9.

Ekiert H, Pajor J, Klin P, Rzepiela A, Ślesak H, Szopa A. Significance of Artemisia Vulgaris L. (Common Mugwort) in the History of Medicine and Its Possible Contemporary Applications Substantiated by Phytochemical and Pharmacological Studies. Molecules. 2020 Sep 25;25(19):4415. doi: 10.3390/molecules25194415. PMID: 32992959; PMCID: PMC7583039.

One of North America's foremost experts on holistic medicine incorporating Western, Ayurveda and Traditional Chinese Medicine, Karta Purkh Singh Khalsa, says dong quai is the most widely used herb in Chinese medicine, and one of the most widely used herbs in the world. He classes dong quai as a long‑term, slow acting tonic remedy. He suggests that due to the hormonal effect it should not be taken until a person is reproductive, so it can be started at puberty. “Then we can start with a very, very small dose taken for the next hundred years every single day…It’s used very casually. It’s cooked into soup. It’s used as a tea. Grandma gives it to all her granddaughters every day,” he says.

Also called ‘female ginseng’, because it is an important herb for the uterus, dong quai is renowned for its use in the treatment of a wide variety of gynaecological conditions and menstrual disorders including endometriosis, amenorrhea, dysmenorrhea, irregular menstruation, recovery from childbirth and menopausal symptoms (especially hot flushes).

Although dong quai is known as the best Chinese tonic herb for women it can be used for both men and women for strengthening the blood, for heart conditions, high blood pressure, inflammation, headache, infections, nerve pain and liver problems. It is the most highly valued blood tonic in the East and has general and non-specific effects on the blood and circulation. Traditionally it is used to regulate the period and to enhance the fertility of women who are blood deficient.

References

Khalsa KP. Relax, Relax, Part 5: Stress and Anxiety Solutions. Natural Solutions for Stress, Anxiety, and Inflammation. LearningHerbs.com c2019 (accessed 7 Nov 2022). Available from https://herbmentormedia.s3-us-west-1.amazonaws.com/Courses/Relax/Relax-KP-Khalsa-Part-4-Transcript.pdf

Trickey R. Women, Hormones and the Menstrual Cycle. 3rd edn. Fairfield: Melbourne Holistic Health Group. 2011. p. 426

Trickey R. Women, Hormones and the Menstrual Cycle. 3rd edn. Fairfield: Melbourne Holistic Health Group. 2011. p. 427

Due to a shortage of butternut raw material from the recent harvest out of the USA, owing in part to limited pickers, we would like to provide you with some alternative herbs. 

Butternut is a species of walnut also known as white walnut, which is a cousin to black walnut (Juglans nigra: this herb has the same procurement issues). It is a mild cathartic (a purgative with a stronger effect than a laxative) for chronic constipation, gently encouraging regular bowel movements, and is often used as a vermifuge (used to destroy or eject worms in the intestine). It is especially beneficial when combined with a carminative herb such as angelica (Angelica archangelica), fennel (Foeniculum vulgare) or ginger (Zingiber officinale). It is used for constipation due to weakness or paralysis of the muscles of the colon and rectum, to stimulate liver function in congestive digestive disorders and for skin diseases, such as dermatitis, associated with sluggish bowel and/or liver. 

Aloes (Aloe ferox): “Aloes” is the generic name for the solid residue obtained by boiling and cooling the latex of Aloe ferox, its hybrids and A. vera (also known as A. barbadensis). The latex, found in cells in the margins of the leaves, is mainly used for its anthraquinone laxative effect. Traditionally it was used as a warming and stimulating purgative and vermifuge. Aloes has been used as a cathartic, stomachic (to tone the stomach and improve its function), emmenagogue and anthelmintic (medicines that are used for treatment of infections with parasitic worms including vermifuges) and more recently for the treatment of diseases of the immune system.

Buckthorn (Rhamnus frangula): Buckthorn has been used in traditional European medicine as a laxative and cathartic, and also as a general tonic. It is particularly useful as a gentle purgative in chronic constipation and as a digestive stimulant. As a laxative buckthorn is not as powerful as senna pods (Senna alexandrina) or aloes and is slightly more effective than rhubarb (Rheum palmatum).

Cascara sagrada (Frangula purshiana): Cascara sagrada (a close European cousin of buckthorn) is best known as an effective stimulating laxative used for chronic constipation, colitis, digestive complaints, haemorrhoids, liver problems and jaundice. Traditionally it was considered suitable for delicate and elderly people. It is a medium strength yet gentle laxative, somewhat weaker than aloes, rhubarb and senna pods, which can move the bowel without griping (although the addition of carminatives is still recommended).

Rhubarb (Rheum palmatum): Also known as Chinese rhubarb (Da Huang), rhubarb has a purgative action. It was primarily used in traditional medicine as a stimulant laxative to treat constipation. At low doses it is said to act as an antidiarrhoeal because of the tannin components whereas at higher doses it exerts a cathartic action. Rhubarb also has an astringent effect, making it a true gut cleanser, as it can firstly remove waste and then astringe the system with its antiseptic properties. To avoid any griping it is recommended to take rhubarb with carminatives.

References

Steenkamp V, Stewart MJ. Medicinal Applications and Toxicological Activities of Aloe. Products, Pharmaceutical Biology. 2007;45:5, 411-420, DOI: 10.1080/13880200701215307

Bhaludra CSS, Bethapudi RR, Murugulla AC, Pullagummi C, Latha T, Venkatesh K, et al. Cultivation, Phytochemical Studies, Biological Activities and Medicinal Uses of Aloe ferox, Grandfather of Aloes an Important Amazing Medicinal Plant. International Journal of Pharmacology. 2013;9: 405-415.

Grieve M. A Modern Herbal. Middlesex: Penguin Books, 1978. p. 136.

Mills S. The Essential Book of Herbal Medicine. Penguin:London. 1991. p.471

Weiss R. Herbal Medicine.Stuttgart: Thieme, 2001. p. 110-11.

Rogers M. Cascara Sagrada. (updated; accessed 2 May 2022). Herbalpedia The Herb Growing & Marketing Network c2014. Available from https://s3-us-west-1.amazonaws.com/herbmentormedia/Articles/PDF/Herbalpedia/herbalpedia-cascara-sagrada.pdf

Mills S. The Essential Book of Herbal Medicine. Penguin:London. 1991. p.445

Hoffmann D. Medical Herbalism. Rochester: Healing Arts Press. 2003. p. 577

Wood M. The Book of Herbal Wisdom. California:North Atlantic Books. 1997.

A flowering plant in the mint family, with densely felted hairs on the leaves, white horehound is primarily used for the treatment of respiratory and gastrointestinal disorders. In the English language the name horehound comes from the Old English words har and hune, meaning downy plant. It was the principal ingredient in the enslaved man Dr Caesar’s antidote for poisons. In the spring of 1750, the USA’s South Carolina General Assembly purchased the freedom of Dr Caesar because it was believed he possessed life-saving medical knowledge. The white minority of South Carolina’s early population were terrified of being secretly poisoned by the enslaved people who prepared their meals and sought remedies that might save them. In return for his emancipation Caesar divulged to a committee of white legislators his secret antidote for poisons and snakebites, prepared from a combination of familiar plants found across the colonial landscape. This simple decoction earned him immortal fame in South Carolina and beyond. The two main ingredients that Caesar employed were white horehound and ribwort (Plantago lanceolata).

White horehound has long been noted for its efficacy in lung troubles and cough. As a gentle stimulating expectorant it assists in bronchitis, asthma, whooping cough, loss of voice, chesty colds and congestive catarrhal conditions with a non-productive cough. Or as one of the most influential herbalist writers, Nicholas Culpeper, described it in the 19th century “tough phlegm from the chest”.

In A Modern Herbal in 1931, for ‘pectoral remedies’, Maud Grieve combined white horehound with hyssop (Hyssopus officinalis), rue (Ruta graveolens), liquorice (Glycyrrhiza glabra) and marshmallow (Althaea officinalis). She also says it is very useful for children’s cough and croup and helps as a “corrective of the stomach”. A bitter action stimulates the flow and secretion of bile from the gallbladder aiding digestion. It is useful for dyspepsia, easing bloating and gas, and acts as a vermifuge. This bitter plant has been used as a substitute for hops (Humulus lupulus) in beer breweries.

References

Butler N. Doctor Caesar and His Antidote for Poison in 1750. Charleston County Public Library c2022. (updated 12 Feb 2021; accessed 3 Nov 2022). Available from https://www.ccpl.org/charleston-time-machine/doctor-caesar-and-his-antidote-poison-1750

Aćimović M, Jeremić K, Salaj N, Gavarić N, Kiprovski B, Sikora V, Zeremski T. Marrubium vulgare L.: A Phytochemical and Pharmacological Overview. Molecules. 2020 Jun 24;25(12):2898. doi: 10.3390/molecules25122898. PMID: 32599693; PMCID: PMC7355696.

Culpeper N. Culpeper’s Complete Herbal and English physician. Magna Books: Leicester 1981 (original edition published 1826). p. 76.

Hoffmann D. Medical Herbalism. Rochester: Healing Arts Press. 2003. p. 565

Rezgui M, Basma M, Neng N, Nogueira JM, Bettaieb Ben-Kaab L, Machado Araújo ME. Evaluation of Marrubium vulgare Growing Wild in Tunisia for Its Potential as a Dietary Supplement. Foods. 2021; 10(11):2864. https://doi.org/10.3390/foods10112864

[vi] Grieve M. A Modern Herbal. Penguin:London; 1980. p. 416

The tall, majestic feathery fronds of fennel stand out from roadsides imparting a sweet aniseed scent however it’s the richly aromatic seeds of this wild weed that are an ancient digestive remedy. Fennel’s carminative action means it is often applied to treat mild spasmodic gastrointestinal complaints such as flatulence, hiccupping, indigestion, colic, bloating, heartburn and intestinal cramps, especially in children and infants (it is an ingredient in gripe water for infant colic). This explains why eating raw fennel seeds before or after a meal is common in many Asian cultures.

Fennel is a useful women’s remedy, and is a well-known galactagogue, used to promote the flow of breast milk. Throughout European tradition it has been highly valued for increasing milk production in both humans and other mammals, such as farm animals. When taken by the mother the volatile oils will pass to the baby to soothe digestive troubles. It has also been used to regulate the menstrual cycle and relieve period pains. Its diuretic properties help relieve fluid retention and urinary infections. This action also assists with arthritis and gout.

Interestingly fennel has ancient connections with the Olympic marathon, the ultimate prize for a long-distance runner. The word ‘marathon’ literally means ‘a place full of fennel’ in Ancient Greek. It is believed that the Greek town of Marathon was originally named so because of an abundance of fennel plants in the area. Marathon was the site of the Battle of Marathon in 490 BCE, in which the heavily outnumbered Athenian army defeated the Persians. Legend has it that Pheidippides, a Greek herald at the battle, was sent running from Marathon to Athens to announce the victory which is how the marathon running race was conceived in modern times. Since then the word ‘marathon’ has been applied to anything that’s done for a long time.

Rarely is fennel seen in herbal texts as a nervine however it has been reported to have mood enhancing properties. Herbal writer and nun from the 12th Century, Hildegard von Bingen, said “Fennel forces the spirits into the correct balance of joy.” In line with this, a recent systematic and meta-analysis investigation into the effectiveness of fennel on symptoms among menopausal women found that, based on the two trials, fennel had beneficial effects on some psychological disorders such as anxiety and depression. The researchers said fennel may have an indirect effect in the treatment of sleep disorder through improving depression and anxiety. The women treated with fennel showed reportedly higher sexual function and sexual satisfaction compared to the placebo group.

References

McIntyre A. The Complete Women’s Herbal. London: Gaia Books Limited, 1994. p. 189

Mills S. The Essential Book of Herbal Medicine. Penguin: London. 1991. p.425-6

McIntyre A. The Complete Women’s Herbal. London: Gaia Books Limited, 1994. p. 189

McIntyre A. The Complete Women’s Herbal. London: Gaia Books Limited, 1994. p. 189

Khadivzadeh T, Najafi MN, Kargarfard L, Ghazanfarpour M, Dizavandi FR, Khorsand I. Effect of Fennel on the Health Status of Menopausal Women: A Systematic and Meta-analysis. J Menopausal Med. 2018 Apr;24(1):67-74. doi: 10.6118/jmm.2018.24.1.67. Epub 2018 Apr 30. PMID: 29765930; PMCID: PMC5949311.

Heckels F, Lawton K (The Seed Sistas). The Sensory Herbal Handbook. Watkins: London. 2019. p. 173-4

In the early days of the Herbal Extract Company (late 1980s) one of the best supporters of our founder, Lyndsay Shume, was the matriarch of herbal medicine, the late Dorothy Hall (dec. March 24, 2012). She believed in the Herbal Extract Company herbs and felt she got the best results with them. She told all her students to use our herbs and to this day many of her students are still our best customers. In her eponymous book, Hall says the fragrant culinary herb thyme is powerfully protective and therapeutic. She calls it one of the “big three” of herbal medicine along with sage (Salvia officinalis) and parsley (Petroselinum crispum), adding that “there can never be a sharp cut-off point between culinary herbs and medicinal herbs.”

Thyme is a potent herbal medicine for different kinds of infection, including bacterial and fungal, but especially those in the respiratory and digestive systems. Hall says thyme is almost equal to garlic (Allium sativum) as an antiseptic herb and as a carminative, for dyspepsia and sluggish digestion, it ranks with chamomile (Matricaria chamomilla). She used thyme to fight off streptococcal throat and lung and kidney infections. “Many tonsillectomies may have been avoided by the use of thyme as a tea, as a gargle, or in an internal mixture,” she said. In the respiratory tract thyme’s expectorant, antispasmodic and antiseptic properties make it useful for any respiratory conditions characterised by excess levels of mucus, phlegm or catarrh including influenza, colds, bronchitis, asthma, whooping cough and sinusitis.

So many beneficial effects have been attributed to time that French herbalist and author Fabrice Bardeau proclaimed thyme as “an indispensable plant, which should be consumed to conserve health. Furthermore, if one could replace ones’ morning cup of coffee with an infusion of thyme, you would quickly appreciate its positive effects: animation of spirit, sensation, lightness in the stomach, absence of morning cough, and its euphoriant and tonic effect.”

References

Hall D. Dorothy Hall’s Herbal Medicine. Sydney:Lothian. 1988. p. 289

Hall D. Dorothy Hall’s Herbal Medicine. Sydney:Lothian. 1988. p. 58, 289

Quave, C.L. Quave Research Group Website. Version 11.0, April 2015. Thymus vulgaris L., Lamiaceae by Carly McCabe [Internet]; 2015 [accessed Nov 7 2022]. Available from https://etnobotanica.us/wp-content/uploads/2011/12/Plant-Monograph-Book-4.2013.pdf

No food or drug of today comes close to matching the place of honour that slippery elm held in 18th and 19th century America. The herb was the nation’s leading home remedy for anything in need of soothing. An Eclectic physician Dr Beach reported the numerous uses by Native Americans and declared that "in point of utility, it is of far more value than its weight in gold".  Its common name refers to the slippery consistency the inner bark assumes when it is chewed or mixed with water.

Slippery elm has traditionally been used for a range of ailments, particularly in relation to the mucous membranes, digestive and urinary systems.  The highly demulcent and soothing action of the mucilage was employed in the treatment of stomach ulcers, reflux, diarrhoea and colitis.  Slippery elm was also used for coughs and sore throats, having a soothing, antitussive and reflex demulcent action. 

The reflex action of the mucilage on the mucous membranes of the genitourinary tract meant the herb was also useful in cases of cystitis and bladder irritation.  Topical applications of the powdered inner bark were traditionally used to help heal and soothe skin ulcers, burns, wounds and boils. The herb also has a bulk laxative action and was valuable in providing nutrition during convalescence.  Slippery elm was taken before festivities to avoid "hangover" and before travelling to avoid travel sickness. While containing less mucilage than a water only based extraction, the ethanol and water extract still contains some mucilage. This extract is useful for compounding and compliance in people who are unable to take the powder.

References

HEC monograph

Ivy leaf is a popular ornamental climbing plant native to Europe. As an evergreen it is still green in the depths of winter and, as such, is the mainstay of British Christmas decorations for church along with holly, both celebrated in the traditional British folk Christmas carol “The Holly and the Ivy”.

The traditional European indications for ivy leaf were primarily for the respiratory tract and to this day it is used against diseases of the lower respiratory tract associated with productive cough including the common cold, asthma and acute and chronic bronchitis. In modern times it is administered to improve lung function and symptoms of coughing and expectoration, especially with accompanying obstructive pulmonary complaints and microbial infections. Clinical data supports these indications, especially for children. 

Ivy leaf’s affinity for the respiratory tract begs the question: “Can it be used for COVID-19?” Current recommendations for the self-management of COVID-19 are similar to how symptoms would be treated for seasonal flu. These include self-isolation, rest, hydration and the use of the painkiller paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, in the case of high fever only. Most of the current guidelines do not specifically advise on how to treat cough, one of the main symptoms which, apart from being very debilitating, contributes to the spread of the virus. It is expected that many patients will add other symptomatic/adjuvant treatments such as herbal medicines. A recent study aimed to provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. The researchers concluded that ivy leaf has “safety margins superior to those of reference drugs [paracetamol, ibuprofen and codeine] and enough levels of evidence to merit [its] potential clinical use as [an adjuvant] in the treatment of early/mild cases of COVID-19.”

References

Mandade R J, Choudhuri A, Mashirkar V, Sakarkar D. Analgesic and anti-inflammatory activities of Hedera helix leaf extract. Pharmacie Globale (IJCP) 2010, 4 (07).

Lutsenko Y, Bylka W, BylkaIrena W, Matławska M, Darmohray R. Hedera helix as a medicinal plant. Herba Polonica. January 2010;56(1).

Herbal Medicine: Expanded Commission E Monographs. American Botanical Council. 2000. Published by Integrative Medicine Communications. Available from the American Botanical Council. http://cms.herbalgram.org/expandedE/Ivyleaf.html

Schmidt M, Thomsen M, Schmidt U. Suitability of ivy extract for the treatment of paediatric cough. Phytother Res. 2012 Dec;26(12):1942-7. doi: 10.1002/ptr.4671. Epub 2012 Apr 25.

Silveira D, Prieto-Garcia JM, Boylan F, Estrada O, Fonseca-Bazzo YM, Jamal CM, Magalhães PO, Pereira EO, Tomczyk M, Heinrich M. COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy? Front Pharmacol. 2020 Sep 23;11:581840. doi: 10.3389/fphar.2020.581840. PMID: 33071794; PMCID: PMC7542597.

Treating COVID-19 symptoms at home. Healthdirect Australia. (updated July 2022;accessed 12 Aug 2022). Available from https://www.healthdirect.gov.au/covid-19/treating-symptoms-at-home

Elecampane is a striking and handsome plant crowned with deep yellow-orange open flowers “like a cross between a dandelion and a sunflower”.It has an ancient medicinal reputation and was described by Dioscorides and Pliny in the first and second centuries. Pliny said “let no day pass without eating some of the roots of Enula, considered to help digestion and cause mirth (cheer).” One explanation for the specific epithet helenium comes from the legend of Helen of Troy (she of the face that launched a thousand ships) who was said to be wearing an elecampane flower in her hair when she was abducted from her homeland by the Trojan prince Paris which started the Trojan wars. The legend says that she was so heartbroken to be taken from Sparta that one of these plants emerged wherever her tears fell.

Elecampane is a general warming and stimulating remedy that gets things moving. It has a long history of use as a tonic herb for the respiratory system and is specific to bronchial infections. It is warming and clearing to the lower respiratory system and along with moving stuck mucous, and restoring healthy mucous, it is strongly antimicrobial. While most commonly used for congestion in the lungs it can also be used for stuck mucous in the sinuses or to correct postnasal drip. In addition to being an excellent expectorant it also soothes the tissue irritation and inflammation that results from coughing. Herbalist extraordinaire, the late Dorothy Hall, says “as a ‘chest’ herb, for respiratory improvement, it relieves symptoms as well as treating cause factors. Invaluable.”

In addition to its well-known respiratory properties elecampane supports digestive function and traditionally it was used for all sorts of digestive woes from intestinal parasites to stagnant digestion to imbalanced intestinal flora. World authority on herbal medicine, Simon Mills, mentions that elecampane can be considered like angelica (Angelica archangelica), “as a useful warming digestive tonic, this further supporting its role as a remedy for the infirm and convalescent.” 

References

Hall D. Dorothy Hall’s Herbal Medicine. Sydney:Lothian. 1988. p. 155

Grieve M. A Modern Herbal. Penguin:London; 1980. p. 279

Elecampane. Herbarium [Internet] Herbal Academy. [Accessed Sep 28 2022] Available from https://herbarium.theherbalacademy.com/monographs/#/monograph/3039

Hall D. Dorothy Hall’s Herbal Medicine. Sydney:Lothian. 1988. p. 155

Mills S. The Essential Book of Herbal Medicine. Penguin:London. 1991. p.478

Efficacy of olive leaves on the outcomes of hospitalised COVID-19 patients: A randomised, triple-blinded clinical trial

Olive leaves can improve the clinical status of COVID-19 patients and decrease the length of hospitalisation an October 2022 clinical trial has found. The randomised, triple-blinded trial was conducted in Iran on 141 patients hospitalised with COVID-19 confirmed with a PCR test. The research project investigated the efficacy of olive leaves extract on the vital signs and laboratory parameters of COVID-19 patients. The researchers said the mechanism by which olive leaves fights viruses is not yet fully understood however it may interfere with the attachment of the virus to the target cell and its subsequent engulfment by immune cells.

Eligible patients were allocated to the following groups: intervention A received olive leaves extract (250mg every 12 hours for five days), intervention B received olive leaves extract (500mg every 12 hours for five days), and the control group received placebo (every 12 hours for five days). The outcomes (vital signs, laboratory tests and length of hospitalisation) were compared by group.

Based on the results, olive leaves extract effectively reduced respiratory rate, pulse rate and body temperature, and increased blood oxygen saturation of COVID-19 patients. Furthermore, it decreased erythrocyte sedimentation rate (ESR: used in the clinical field as a non-specific marker of systemic inflammation) and C-reactive protein (CRP: seen in acute infections and inflammatory conditions) levels in COVID-19 patients. The findings also showed that olive leaves extract can shorten the duration of hospitalisation and lead to the early discharge of the patient. There was no difference between the two doses of olive leaves extract (250mg and 500mg) in terms of efficacy. The researchers suggested that further studies, with a larger sample size, be conducted to discover the efficacy of olive leaves in the treatment of COVID-19 patients.

References

Ahmadpour E, Toulabi T, Yadegarinia D, Yarahmadi S, Mohammadi R, Keyvanfar A. Efficacy of olive leaves extract on the outcomes of hospitalized covid-19 patients: A randomized, triple-blinded clinical trial. Explore (NY). 2022 Oct 29:S1550-8307(22)00204-X. doi: 10.1016/j.explore.2022.10.020. Epub ahead of print. PMID: 36319585; PMCID: PMC9617633.