bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of partial auricular skin cancer defects: a review of current techniques
Authors: Noor Anthony , Thomson Neil
Published: April 2023

Purpose of review

To discuss the principles of auricular reconstruction and review recently published literature in the field.

Recent findings

Auricular reconstruction poses several challenges to the surgeon aiming to restore form and function following skin cancer resection. Various techniques have been described in the literature with many modifications also reported to address their shortcomings. An algorithmic approach based on the location and composition of the defect is recommended. In many instances, more than one technique can be used, and the operating surgeon should be familiar with these to determine the optimal approach for the individual patient.

This review highlights the updates in well established techniques as well as modern modifications. Furthermore, a framework for decision-making in auricular reconstruction is presented.
Update on congenital ear molding
Authors: Roby Brianne Barnett , Woods Tiffanie , Chinnadurai Sivakumar
Published: April 2023

Purpose of review

Congenital ear deformities are characterized by distorted, but still present, landmarks of the auricle. Interventions include early treatment with ear molding or delayed surgical treatment. The purpose of this review is to provide an update on the latest information related to ear molding for congenital ear deformities.

Recent findings

Various ear molding techniques date back to the 1980s, but with the availability of commercially available molding systems, interest and use has blossomed in recent years. As more longitudinal research results are obtained, ear molding has been proven to be a highly effective treatment, although the best technique and length of treatment remains unclear.

While it is clear that earlier intervention is ideal, due to lack of public awareness, patients often present later, and it remains controversial what age to offer ear molding interventions to and still expect success. Ear molding interventions are becoming increasingly covered by insurance due to evidence of preventing long-term psychological morbidities and the need for future surgical interventions.
Accuracy of Anorectal Manometry to Detect the Rectoanal Inhibitory Reflex in Children: Awake Versus Under General Anesthesia
Authors: Baaleman Desiree F. , Mishra Samir , Koppen Ilan J.N. , Oors Jac. M. , Benninga Marc A. , Bali Neetu , Vaz Karla H. , Yacob Desale , Di Lorenzo Carlo , Lu Peter L.
Published: April 2023

Objectives:

Our objective was to investigate if there is a difference in the detection of the rectoanal inhibitory reflex (RAIR) when an anorectal manometry (ARM) is performed awake or under general anesthesia.

Methods:

A retrospective review of ARM studies was performed to identify children who had undergone ARMs both while awake and under general anesthesia. We compared ARM outcomes including the detection of the RAIR and anal canal resting pressure.

Results:

Thirty-four children had received ARMs both while awake and under general anesthesia (53% female, median age at first ARM 7.5 years [range 3–18 years]). In 9 of 34 (26%) children the RAIR was solely identified during ARM under general anesthesia and not during ARM while awake. In 6 of 9 (66%) this was unrelated to the balloon volumes used during balloon inflations. In 4 of 34 (12%) children, assessment of the RAIR was inconclusive during ARM under general anesthesia due to too low, or loss of anal canal pressure. In 2 of those children, ARMs while awake showed presence of a RAIR. Anal canal resting pressures were higher during ARM while awake versus ARM under general anesthesia (median 70 [interquartile range, IQR 59–85] vs 46 mmHg [IQR 36–65] respectively, P < 0.001).

Conclusions:

General anesthesia may affect the detection of a RAIR in 2 ways. On the one hand, it may facilitate better visualization in children in whom a RAIR could not be visualized while awake. On the other hand, it may cause a loss of anal canal pressure resulting in an inconclusive test result.
Effect of different constraint-induced movement therapy protocols on recovery of stroke survivors with upper extremity dysfunction: a systematic review and network meta-analysis
Authors: Gao Qian , Zhang Yasu , Long Junzi , Pan Mengyang , Wang Jing , Yang Fangjie
Published: April 2023

We aimed to assess and rank comparative efficacy of different constraint-induced movement therapy (CIMT) protocols on motor function of upper extremity and activities of daily living (ADL) in stroke survivors. A comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library to identify randomized controlled trials on CIMT. Included studies were evaluated using the revised Cochrane risk of bias tool. Then a random-effects network meta-analysis was performed within a frequentist framework using Stata v16.0. Of the 1150 studies retrieved, 44 studies with 1779 participants were included. In terms of motor recovery of upper extremity, CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked as the most effective intervention for the improvement of the Fugl-Meyer Assessment-Upper Extremity and the Action Research Arm Test score. In terms of ADL improvement, constraining the less affected arm for at least 4 h but no more than 6 h per day in CIMT combined with trunk restraint, was found to significantly improve the Motor Activity Log of quality of movement scale and amount of use scale score. The protocol of CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked the highest in this analysis and might be considered in practice.
Nonautoimmune overt hypothyroidism in the early stages of nephrotic syndrome: a case report from Somalia
Authors: Adan Abdisamad Mohamed , Siyad Mohamed Osman , Jeele Mohamed Osman Omar
Published: April 2023

Introduction:

Nephrotic syndrome (NS) was first characterized in 1827 as the occurrence of proteinuria greater than or equal to 3.5 g/24 h, hypoalbuminemia (albumin≤3.0 g/dl), peripheral edema, hyperlipidemia, lipiduria caused by increased permeability of the renal glomerulus. Persistent proteinuria will eventually lead to hypothyroidism.

Case presentation:

In the presenting case, we reported a 26-year-old male patient with no known history of chronic disease who presented to the emergency department with a complaint of 1-week generalized edema, nausea, fatigue, and generalized ache in the extremities. He was diagnosed with NS complicated by hypothyroidism and was hospitalized for 3 weeks. After 3 weeks of treatment and close monitoring, the patient’s clinical condition and laboratory investigations were improved, and was discharged in good health.

Conclusion:

Hypothyroidism in the early stages of NS is a rare entity which may be encountered and physicians should be aware that hypothyroidism can be seen at any stage of NS.
Comparative study of wound infection between elective and emergency abdominal surgeries: a retrospective cohort study
Authors: Jadoon Sarosh Khan , Khan Raja Muhammad Ijaz , Khan Taufeeq Ahmed , Akhtar Naheed , Qayyum Yasir , Kumar Kamlesh , Kumar Rahul Robaish , Aarti  , Shahab Ramsha , Asghar Muhammad Sohaib
Published: April 2023

Objective:

The objective of this study was to determine the frequency of wound infection among patients with abdominal surgeries and to compare the surgical site infection following elective versus emergency abdominal surgeries in a tertiary care hospital.

Subjects and methods:

All patients who fulfilled the inclusion criteria in the Department of General Surgery were included in the study. After taking informed written consent history was taken, clinical examination and patients were divided into two groups: group A (elective abdominal surgery) and group B (emergency abdominal surgery), patients in both groups were compared for the outcome that is surgical site infection.

Result:

A total of 140 patients who underwent abdominal surgery were included. Wound infection in abdominal surgeries was noted in 26 patients (18.6%), in group A wound infection was noted in 7 (5%), while in group B wound infection was seen in 19 (13.6%).

Conclusion:

The rate of wound infection in patients with abdominal surgeries was not low among the study population and the rate of wound infection was higher in emergency abdominal surgeries as compared with elective abdominal surgeries.
Navigating the journey of multiple sclerosis management in Africa, overcoming hurdles and harnessing opportunities: a review
Authors: Aderinto Nicholas , Muili AbdulBasit O. , Opanike Joshua
Published: April 2023

Multiple sclerosis (MS) is a chronic, debilitating condition affecting many African people. However, the management of MS in Africa is often inadequate, and there is a need to improve the care and support provided to patients. This paper aims to identify the challenges and opportunities in navigating the journey of MS management in Africa. MS management’s main challenges in Africa include a lack of awareness and education about the disease, limited access to diagnostic tools and treatments, and inadequate care coordination. However, by increasing awareness and education about MS, improving access to diagnostic tools and treatments, fostering multidisciplinary collaborations, encouraging and supporting research on MS in Africa, and collaborating with regional and international organizations to share knowledge and resources, it is possible to improve the management of the disease and improve the lives of those affected by MS in Africa. This paper concludes that improving the management of MS in Africa requires a concerted effort from all stakeholders, including healthcare professionals, policymakers, and international organizations. Collaboration and sharing of knowledge and resources are crucial to ensure that patients receive the best possible care and support.
Benign inoperable tracheal stenosis in COVID versus non-COVID patients at the pandemic epicenter: a case series
Authors: Perwaiz Muhammad , Durrance Richard , Bogart Michael , obata Reiichiro , Bradley Ellen C.
Published: April 2023

Background:

The COVID-19 pandemic has exponentially expanded the number of patients requiring treatment for chronic respiratory failure. One consequence is an increase in the number of patients requiring intubation and mechanical ventilation. Benign inoperable tracheal stenosis presents a challenge, especially in COVID-19 patients.

Methods:

We describe a case series of 15 patients with Benign inoperable tracheal stenosis treated with interventional bronchoscopy over a 15-month period. These patients were divided into two groups, COVID and non-COVID. We used an electrocautery snare as an electrocautery knife to cut the stenotic segment followed by four injections of 1 mg submucosal Decadron via a Wang needle. Patients were subsequently followed by the pulmonary clinic. Institutional review board approval was not required as per our institutional policy for a retrospective case series.

Results:

There was a high degree of success with this intervention, with a low rate of recurrence. We also noticed the following differences between the two subgroups. COVID tracheal stenosis was longer in length, had a higher percentage of cartilage involvement, and was located more distal to cords than the non-COVID group. The median age was younger in the COVID group.

Conclusions:

COVID pandemic an enormous number of intubations and tracheotomies have been performed. As a result, there will be an increased prevalence of tracheal stenosis. Most of these cases can be effectively treated with surgery. Dealing with complex inoperable cases remains a dilemma. Our case series/research article is an attempt to provide an easy technique with a high cure rate.
Contrasting Metacognitive, Emotion Recognition and Alexithymia Profiles in Bulimia, Anorexia, and Schizophrenia
Authors: Lysaker Paul H. , Chernov Nikita , Moiseeva Tatyana , Sozinova Marta , Dmitryeva Nadezhda , Makarova Anastasiya , Kukla Marina , Myers Evan , Karpenko Olga , Kostyuk Georgiy
Published: April 2023

Alexithymia, or deficits in emotion recognition, and metacognitive capacity have been noted both in psychosis and eating disorders and potentially linked to psychopathology. This study sought to compare levels of impairments in these phenomena and their associations with psychopathology in groups with eating disorders and psychosis. Participants with diagnoses of a schizophrenia spectrum disorder (SSD; n = 53), anorexia (n = 40), or bulimia (n = 40) were recruited from outpatient clinics. Alexithymia was measured with the Toronto Alexithymia Scale; emotion recognition, with the Ekman Faces Test; and metacognition, with the Metacognitive Assessment Scale–Abbreviated. Psychopathology was measured with the Eating Attitudes Test, Body Image Questionnaire, and Positive and Negative Syndrome Scale. Results indicated that the SSD group had significantly poorer metacognitive function than either eating disorder group. Metacognition was related to body image in the anorexia group and a range of different forms of general psychopathology in the bulimia group. Alexithymia was related to eating disorder behaviors in the bulimia group.
Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review
Authors: Alruwaii Zainab I. , Montgomery Elizabeth A.
Published: April 2023

Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.
Structured Callouts, the Shared Mental Model, and Teamwork
Authors: Wolfgang Matthew , Labudde Emily J. , Ruff Kristen , Geis Gary , Frey Mary , Boyd Stephanie , Harun Nusrat , Kerrey Benjamin T.
Published: April 2023

Objectives

The shared mental model is essential to high-quality resuscitations. A structured callout (SCO) is often performed to establish the shared mental model, but the literature on SCOs is limited. The objectives of this study are to describe performance of SCOs during pediatric medical emergencies and to determine whether a SCO is associated with better teamwork.

Methods

This was a retrospective study in the resuscitation area of an academic pediatric emergency department, where performance of a SCO is a standard expectation. Only medical or nontrauma patients were eligible for inclusion. Data collection was performed by structured video review by 2 observers and verified by a third blinded observer. A SCO was defined as team leader (Pediatric Emergency Medicine fellow or faculty physician) verbalization of at least 1 element of the patient history/examination or an assessment of patient physiology and 1 element of the diagnostic or therapeutic plan. We independently measured teamwork using the Teamwork Emergency Assessment Measure (TEAM) tool.

Results

We reviewed 60 patient encounters from the pediatric emergency department resuscitation area between April 2018 and June 2020. Median patient age was 6 years; the team leader was a Pediatric Emergency Medicine fellow in 55% of encounters. The physician team leader performed a SCO in 38 (63%) of patient encounters. The TEAM scores were collected for 46 encounters. Mean TEAM score (SD) was 42.3 (1.7) in patients with a SCO compared with 40.0 (3.0) in those without a SCO (P = 0.007).

Conclusions

Performance of a SCO was associated with better teamwork, but the difference was of unclear clinical significance.
Assisted Partner Notification Services Are Safe and Effective as They Are Brought to Scale in Mozambique
Authors: Golden Matthew R. , Mamudo Allend , Vio Ferruccio , Branigan Erin , Paredes Zulmira , Maiela Adelina , Augusto Orvalho , Couto Aleny , Amane Guita , Chicuecue Noela , Wate Joaquim , Mudender Florindo
Published: April 2023

Background:

The World Health Organization recommends that persons diagnosed with HIV be offered assisted partner notification services (APS). There are limited data on the safety of APS as implemented in public health programs.

Setting:

Three public health centers in Maputo, Mozambique, 2016–2019.

Methods:

Counselors offered APS to persons with newly diagnosed HIV and, as part of a program evaluation, prospectively assessed the occurrence of adverse events (AEs), including (1) pushing, abandonment, or yelling; (2) being hit; and (3) loss of financial support or being expelled from the house.

Results:

Eighteen thousand nine hundred sixty-five persons tested HIV-positive in the 3 clinics, 13,475 (71%) were evaluated for APS eligibility, 9314 were eligible and offered APS, and 9219 received APS. Index cases (ICs) named 8933 partners without a previous HIV diagnosis, of whom 6137 tested and 3367 (55%) were diagnosed with HIV (case-finding index = 0.36). APS counselors collected follow-up data from 6680 (95%) of 7034 index cases who had untested partners who were subsequently notified; 78 (1.2%) experienced an AE. Among 270 ICs who reported a fear of AEs at their initial APS interview, 211 (78%) notified ≥1 sex partner, of whom 5 (2.4%) experienced an AE. Experiencing an AE was associated with fear of loss of support (odds ratio [OR] 4.28; 95% confidence interval [CI]: 1.50 to 12.19) and having a partner who was notified, but not tested (OR 3.47; 95% CI: 1.93 to 6.26).

Conclusion:

Case-finding through APS in Mozambique is high and AEs after APS are uncommon. Most ICs with a fear of AEs still elect to notify partners with few experiencing AEs.
Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality
Authors: Sperry Jason L , Cotton Bryan A , Luther James F , Cannon Jeremy W , Schreiber Martin A , Moore Ernest E , Namias Nicholas , Minei Joseph P , Wisniewski Stephen R , Guyette Frank X ,   the Shock, Whole Blood, and Assessment of Traumatic Brain Injury (SWAT) Study Group
Published: April 2023

BACKGROUND:

Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation.

STUDY DESIGN:

A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors.

RESULTS:

A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with >70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03).

CONCLUSIONS:

Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury.
Draft genome sequences for ten strains of Xanthomonas species that have phylogenomic importance
Authors: Harrison Jamie , Hussain Rana Muhammad Fraz , Greer Shannon F. , Ntoukakis Vardis , Aspin Andrew , Vicente Joana G. , Grant Murray , Studholme David J.
Published: April 2023

Here we report draft-quality genome sequences for pathotype strains of eight plant-pathogenic bacterial pathovars: Xanthomonas campestris pv. asclepiadis, X. campestris pv. cannae, X. campestris pv. esculenti, X. campestris pv. nigromaculans, X. campestris pv. parthenii, X. campestris pv. phormiicola, X. campestris pv. zinniae and X. dyei pv. eucalypti (= X. campestris pv. eucalypti). We also sequenced the type strain of species X. melonis and the unclassified Xanthomonas strain NCPPB 1067. These data will be useful for phylogenomic and taxonomic studies, filling some important gaps in sequence coverage of Xanthomonas phylogenetic diversity. We include representatives of previously under-sequenced pathovars and species-level clades. Furthermore, these genome sequences may be useful in elucidating the molecular basis for important phenotypes such as biosynthesis of coronatine-related toxins and degradation of fungal toxin cercosporin.
Proposal of Christiangramia gen. nov., Neomelitea gen. nov. and Nicoliella gen. nov. as replacement names for the illegitimate prokaryotic generic names Gramella Nedashkovskaya et al. 2005, Melitea Urios et al. 2008 and Nicolia Oliphant et al. 2022, respectively
Authors: Deshmukh Umakant Bhoopati , Oren Aharon
Published: April 2023

The prokaryotic generic names

Gramella

Nedashkovskaya et al. 2005,

Melitea

Urios et al. 2008 and Nicolia Oliphant et al. 2022 are illegitimate because they are later homonyms of the names

Gramella

Kozur 1971, a genus of fossil ostracods,

Melitea

Péron and Lesueur 1810 (Scyphozoa, Cnidaria),

Melitea

Lamouroux 1812 (Anthozoa, Cnidaria), Nicolia Unger 1842, an extinct plant genus, and Nicolia Gibson-Smith and Gibson-Smith 1979 (Bivalvia, Mollusca), respectively (Principle 2 and Rule 51b(4) of the International Code of Nomenclature of Prokaryotes). For

Gramella

, we therefore propose the replacement generic name Christiangramia with type species Christiangramia echinicola comb. nov. and we propose the reclassification of 18 other species of

Gramella

in the genus Christiangramia as new combinations. In addition, we propose the replacement generic names Neomelitea with type species Neomelitea salexigens comb. nov. and Nicoliella with type species Nicoliella spurrieriana comb. nov.
Rathayibacter rubneri sp. nov. isolated from Allium cepa var. Rijnsburger, an onion landrace
Authors: Stoll Dominic A. , Grimmler Christina , Hetzer Birgit , Kulling Sabine E. , Huch Melanie
Published: April 2023

The novel, aerobic, Gram-stain-positive, rod-shaped bacterial strain, ZW T2_19T, was isolated from an onion sample (Allium cepa var. Rijnsburger). Analyses of the 16S rRNA gene sequence revealed that ZW T2_19T represented a member of the genus

Rathayibacter

but may represent a novel species of this genus. Analyses of the whole draft genome sequences, i.e. digital DNA–DNA hybridisation (dDDH) and average nucleotide identity (ANI) of ZW T2_19T and all type strains of species of the genus

Rathayibacter

confirmed that ZW T2_19T represents a novel species of the genus

Rathayibacter

. The genome size of ZW T2_19T is 4.01 Mbp and the DNA G+C content is 71.8 mol%. Glucose, mannose, rhamnose and ribose were detected as whole-cell sugars of ZW T2_19T. The major respiratory quinone of ZW T2_19T is menaquinone MK-10, at 78.9 %. The detected peptidoglycan type in ZW T2_19T is a variant of type B2γ with {Gly} [l-diaminobutyric acid (l-DAB)/l-homoserine (l-Hse)] d-Glu-l-DAB. Polar lipids in ZW T2_19T consisted of one diphosphatidylglycerol, one phosphatidylglycerol, seven glycolipids, one phospholipid and one lipid. The fatty acid profile of ZW T2_19T predominantly consisted of anteiso-C15 : 0 (53 %), iso-C16 : 0 (21 %) and anteiso-C17 : 0 (18 %). In addition, API 20NE, API 50CH, API Coryne, API ZYM, antibiotic susceptibility, haemolysis and growth at different temperatures and with different supplements was investigated. On the basis of the results obtained using this polyphasic approach, including molecular, phenotypic and biochemical analyses, we propose the novel species Rathayibacter rubneri with the type and only strain ZW T2_19T (= DSM 114294T = LMG 32700T).
PROFILE AND TRAINING ON GENDER IDENTITY AMONG HEALTH PROFESSIONALS IN THE CAETÉ REGION IN THE EASTERN AMAZON
Authors: Barbosa Pedro Renan Nascimento , Fernandes Roseane do Socorro da Silva Matos , Nunes Erica Feio Carneiro , Rodrigues Cibele Nazaré Câmara
Published: April 2023

Background

The National Policy on Integral Health of Lesbians, Gays, Bisexuals, Transvestites, and Transsexuals (PNSILGBT+) aims to eliminate discrimination and institutional prejudice in public health services, with emphasis on training and enabling professionals to assist in the care of this population. However, for transsexuals and transvestites, this access continues to be neglected.

Aim

To determine the profile of health professionals, their academic-professional training in health, and their knowledge about the specificities of gender identity.

Methods

This is a cross-sectional, observational, quantitative survey conducted with health professionals working in the Caeté Region. Data were collected using a semi-structured questionnaire, which was applied online via Google Forms in the period from March 2021 to August 2021.

Outcomes

Epidemiological profile, academic education, area of practice, and knowledge about gender identity were predictors for the descriptive analysis.

Results

The sample consisted of 73 participants: 82.19% female, 100% cisgender, with a mean age of 32.37±7.80 years, and the majority self-declared as Catholic (65.75%). The largest number of health professionals were in Nursing (34.24%), practicing in Tertiary Care (50.68%), with an average time of service of 6.24±6.30 years. The volunteers reported that they did not understand the difference between cisgender and transgender people (57.53%), admitting that they had not received any training on gender identity or the healthcare of Lesbians, Gays, Bisexuals, Transvestites, and Transsexuals (LGBT)+ people (79.45%). However, 87.67% understood the importance of training on this subject for the healthcare of this population.

Clinical Implications

This study demonstrates the need for continued trainings on gender identity, health and care of the LGBT+ population, with a focus on transgender people, to eliminate institutional bias.

Strengths and limitations

The research was based on the search for professionals’ knowledge about gender identity, even in healthcare in a region in the interior of the Amazon, however it did not reach the preterit sample n, but it was important for the debate between the professionals reached and the institutions and their managers.

Conclusion

The academic training and professional development of health professionals are still lacking when it comes to the theme studied; a fundamental point needed to comply with the National Curricular Guidelines (NCDs) for courses in health, National Policy for Professional Development, and in particular, the PNSILGBT+.
Effectiveness of mHealth Interventions for Blood Pressure Control among Vulnerable Populations: A Systematic Review
Authors: Azar Kristen M.J. , Zoken Yael , Cooper-DeHoff Rhonda M. , Fontil Valy , Madelaine F. Modrow , Nasrallah Catherine , Pletcher Mark J.
Published: April 2023

Social determinants of health and sociodemographic differences place some individuals at higher risk for hypertension leading to persisting disparities. While mobile health (mHealth) offers a promising approach to facilitate blood pressure (BP) management, it remains unclear which interventions are most effective for addressing disparities in hypertension control. We reviewed the current literature to examine whether mHealth interventions for BP control are effective in improving BP control in populations vulnerable to disparities in hypertension. We conducted a systematic review using multiple databases from January 1, 2009 through December 31, 2020. For inclusion, participants must have elevated blood pressure and belong to a sociodemographic group with known disparities in hypertension. We also tracked specific characteristics of each intervention. Out of the eight articles that met our eligibility criteria for inclusion, five were published in 2018 to 2020. Only four demonstrated a significant reduction in BP and all those interventions incorporated care teams. Despite some evidence of the effectiveness of mHealth interventions for improving BP control among vulnerable groups, more effective interventions are needed, and the quality of studies is overall low. Further research is needed to find the most effective ways to engage diverse communities with mHealth solutions to improve BP control.
A critical role for PLCG1 in RAS activation by BCR-ABL1 and FLT3-ITD
Authors: Szeto May Yee , Mase Anjeli , Kulhanek Kayla , Banerjee Saikat , Rubio Ignacio , Roose Jeroen , Shah Neil
Published: April 2023

Myeloid leukemias are frequently associated with pathologically activating mutations in tyrosine kinases [BCR-ABL1 in chronic myeloid leukemia (CML); FLT3 juxtamembrane internal tandem duplication (ITD) mutations, FLT3 and KIT activation loop mutations in acute myeloid leukemia (AML)]. Mutations in these kinases activate RAS, which initiates multiple downstream signaling pathways that regulate cell proliferation, differentiation, and apoptosis. The mechanisms whereby RAS is activated by these kinases is incompletely understood, and a better understanding of the molecular mediators involved in RAS activation may uncover new therapeutic strategies. Here we identify a biologically and therapeutically important novel mechanism whereby BCR-ABL1 and FLT3-ITD activate the critical downstream effector RAS in part through phospholipase C gamma-1 (PLCG1). PLCG1 knockout decreases proliferation of CML and FLT3-ITD-expressing AML cells, reduces RAS nucleotide exchange factor activity, and increases sensitivity of CML cells to BCR-ABL1 tyrosine kinase inhibitors (TKIs). Collectively, these studies suggest that PLCG1 inhibition may augment clinical responses to BCR-ABL1 and FLT3 TKIs in CML and AML.
Survey of rice (Oryza sativaL.) production ecosystems in northern Ghana confirms low risk of exposure to potential toxic elements from local grain consumption
Authors: Adomako Eureka E. A. , Aboagye-Ghunney Kow , Owusu Prince
Published: April 2023

Expanding local rice production to meet consumer demand is a priority action under the Government of Ghana’s Planting for Food and Jobs initiative. While studies on yield-enhancing interventions including seed improvement and fertilizer management abound, fewer studies focus on food safety issues such as the potential toxic element status of the production ecosystems. This study was, therefore, conducted to bridge the knowledge gap. Chemical analyses were conducted on water, soil and rice grain samples from rainfed upland, rainfed lowland and irrigated lowland rice ecosystems in the Northern and Upper East regions of the country. Statistical analysis of the data showed that soil and rice grain arsenic concentrations were significantly higher (P < 0.001) in the Upper East region. In the Northern region, mean cadmium concentration in rice grains from the irrigated lowland fields (0.023 ± 0.003 mg/kg) was significantly higher than in grains from the rainfed fields. All recorded concentrations of rice grain arsenic, cadmium and lead were, however, within permissible limits, indicating a low risk of dietary exposure. The observed differences in concentrations within and between regions suggest that soil texture and other geogenic factors could influence the potential toxic element status of the rice production ecosystems. Regular monitoring is, therefore, recommended to maintain the safety of Ghana’s locally produced rice for human consumption.
Genetically Determined Blood Pressure, Antihypertensive Drugs, and Genes with Clinical Outcome after Ischemic Stroke: Evidence from Mendelian Randomization
Authors: Liu Hanchen , Zhang Xiaoxi , Zhou Yu , Nguyen Thanh N. , Zhang Lei , Xing Pengfei , Li Zifu , Shen Hongjian , Zhang Yongxin , Hua Weilong , Xu Hongye , Zhu Xuan , Lei Chen , Zuo Qiao , Zhao Rui , Li Qiang , Dai Dongwei , Zhang Yongwei , Xu Yi , Huang Qinghai , Liu Jianmin , Yang Pengfei
Published: April 2023

Background

Observational studies suggest a robust association between blood pressure (BP) and functional outcomes in ischemic stroke patients. We sought to identify novel associations of the genetic basis of 3-month functional outcome after ischemic stroke based on a Mendelian randomization (MR) framework.

Methods

We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3- month favorable functional outcome defined as modified Rankin Scale (mRS) of 0-2. The secondary outcome was excellent 90-day outcome defined as mRS 0-1. The Cochran’s Q statistic in Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses.

Results

Genetic predisposition to higher systolic and diastolic BP was associated with a lower probability of 3-month excellent functional outcome after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59,p=0.014; OR=1.27, 95%CI 1.07-1.51,p=0.006, respectively). Pulse pressure was associated with both excellent and favorable functional outcome (OR=1.05, 95%CI 1.02-1.08,p=0.002; OR=1.04, 95%CI 1.01-1.07,p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB), were significantly associated with improved favorable functional outcome (OR=0.76, 95%CI 0.62-0.94,p=0.009; OR=0.89, 95%CI 0.83-0.97,p=0.005). Proxies for β-blockers, angiotensin receptor blocker (ARB) and thiazides failed to show associations with functional outcome (p>0.05).

Conclusion

We provide evidence for a potential association of genetic predisposition to higher BP with higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcome in ischemic stroke.
Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses
Authors: Lubow Jay , Levoir Lisa M. , Ralph Duncan K. , Belmont Laura , Contreras Maya , Cartwright-Acar Catiana H. , Kikawa Caroline , Kannan Shruthi , Davidson Edgar , Doranz Benjamin J. , Duran Veronica , Sanchez David ER. , Sanz Ana M. , Rosso Fernando , Einav Shirit , Matsen Frederick A. , Goo Leslie
Published: April 2023

Sequential dengue virus (DENV) infections often generate neutralizing antibodies against all four DENV serotypes and sometimes, Zika virus. Characterizing cross-flavivirus broadly neutralizing antibody (bnAb) responses can inform countermeasure strategies that avoid infection enhancement associated with non-neutralizing antibodies. Here, we used single cell transcriptomics to mine the bnAb repertoire following secondary DENV infection. We identified several new bnAbs with comparable or superior breadth and potency to known bnAbs, and with distinct recognition determinants. Unlike all known flavivirus bnAbs, which are IgG1, one newly identified cross-flavivirus bnAb (F25.S02) was derived from IgA1. Both IgG1 and IgA1 versions of F25.S02 and known bnAbs displayed neutralizing activity, but only IgG1 enhanced infection in monocytes expressing IgG and IgA Fc receptors. Moreover, IgG-mediated enhancement of infection was inhibited by IgA1 versions of bnAbs. We demonstrate a role for IgA in flavivirus infection and immunity with implications for vaccine and therapeutic strategies.
Occurrence-based diversity estimation reveals macroecological and conservation knowledge gaps for global woody plants
Authors: Kusumoto Buntarou , Chao Anne , Eiserhardt Wolf L. , Svenning Jens-Christian , Shiono Takayuki , Kubota Yasuhiro
Published: April 2023

Incomplete sampling of species’ geographic distributions has challenged biogeographers for many years to precisely quantify global-scale biodiversity patterns. After correcting for the spatial inequality of sample completeness, we generated a global species diversity map for woody angiosperms (82,974 species, 13,959,780 occurrence records). The estimated diversity demonstrated non-linear latitudinal and longitudinal patterns that were potentially related to region-specific biogeographic factors including current climate, paleoclimate, and topographical factors, while energy availability was the most important predictor at a global level. We identified the areas with potentially high species richness and rarity, but poorly explored, unprotected, and threatened by deforestation: they are distributed mostly at low latitudes across central South America, central Africa, subtropical China, and Indomalayan islands. These priority areas for botanical exploration would help to efficiently fill spatial knowledge gaps for better describing the status of biodiversity and improve the effectiveness of the protected area network for global woody plant conservation.

Teaser

Bias-corrected diversity map based on occurrence records sheds new light on global macroecology and conservation of woody angiosperms.
Time of day and genotype sensitivity adjust molecular responses to temperature stress in sorghum
Authors: Bonnot Titouan , Somayanda Impa , Jagadish S. V. Krishna , Nagel Dawn H
Published: April 2023

Sorghum is one of the four major C4 crops that are considered to be tolerant to environmental extremes. Sorghum shows distinct growth responses to temperature stress depending on the sensitivity of the genetic background. About half of the transcripts in sorghum exhibit diurnal rhythmic expressions emphasizing significant coordination with the environment. However, an understanding of how molecular dynamics contribute to genotype-specific stress responses in the context of the time of day is not known. We examined whether temperature stress and the time of day impact the gene expression dynamics in cold-sensitive and tolerant and heat-sensitive and tolerant sorghum genotypes. We found that time of day is highly influencing the temperature stress responses, which can be explained by the rhythmic expression of most thermo-responsive genes. This effect is more pronounced in thermo-tolerant genotypes, suggesting a stronger regulation of gene expression by the time of day and/or by the circadian clock. Genotypic differences were mostly observed on average gene expression levels, but we identified groups of genes regulated by temperature stress in a time-of-day and genotype-specific manner. These include transcriptional regulators and several members of the Ca2+-binding EF-hand protein family. We hypothesize that expression variation of these genes between genotypes may be responsible for contrasting sensitivities to temperature stress in tolerant vs susceptible sorghum varieties. These findings offer a new opportunity to selectively target specific genes in efforts to develop climate-resilient crops based on their time of day and genotype variation responses to temperature stress.
Functional similarity of non-coding regions is revealed in phylogenetic average motif score representations
Authors: Alam Aqsa , Duncan Andrew G , Mitchell Jennifer A , Moses Alan M
Published: April 2023

Here we frame the cis-regulatory code (that connects the regulatory functions of non-coding regions, such as promoters and UTRs, to their DNA sequences) as a representation building problem. Representation learning has emerged as a new approach to understand function of DNA and proteins, by projecting sequences into high-dimensional feature spaces, where the features are learned from data by a neural network. Inspired by these approaches, we seek to define a feature space where non-coding regions with similar regulatory functions are nearby each other. As a first attempt, we engineered features based on matches to biochemically characterized regulatory motifs in the DNA sequences of non-coding regions. Remarkably, we found that functionally similar promoters and 3’ UTRs could be grouped together in a feature space defined by simple averages of the best match scores in (unaligned) orthologous non-coding regions, which we refer to as phylogenetic average motif scores. Perhaps most important, because this feature space is based on known motifs and not fit to any data, it is fully interpretable and not limited to any particular cell type or experimental context. We find that we can read off known regulatory relationships and evolutionary rewiring from visualizations of phylogenetic average motif score representations, and that predicted regulatory interactions based on neighbors in the feature space are borne out in transcription factor deletion experiments. Phylogenetic averages of match scores to known motifs is a baseline for representation learning applied to non-coding sequences, and may continue to improve as databases of motifs become more complete.
Sexually dimorphic dynamics of the microtubule network in medaka (Oryzias latipes) germ cells
Authors: Kikuchi Mariko , Yoshimoto Miyo , Ishikawa Tokiro , Kanda Yuto , Mori Kazutoshi , Nishimura Toshiya , Tanaka Minoru
Published: April 2023

Oogenesis is the process through which ovarian germ cells enter meiosis and acquire essential characteristics of an egg, such as an increase in follicular size and deposition of maternal factors. In vertebrates, however, the pathways that initiate oogenic processes after germ cell sex determination remain elusive. Here we report a dome-shaped microtubule structure that is maintained during oogenesis. This structure is established in primordial germ cells and maintained in gonocytes and stem-type germ cells in afoxl3-independent manner.dmrt1is required for disruption of the dome structure in differentiating spermatogonia. In addition, the dome structure accumulates mitochondria and Golgi apparatus, and is replaced by the Balbiani body, an oocyte-specific aggregate producing animal-vegetal polarity, suggesting a role for this structure in organelle transfer and oocyte polarization. Our findings show the presence of a pathway regulating a sexually dimorphic microtubule network independent of germ cell feminization byfoxl3.

Summary Statement

A dome-shaped microtubule structure leading to oocyte polarity was identified in germ cells. Genetic pathways involved in the formation and destabilization of the structure during germ cell sex determination were clarified.
BCG Vaccination Policy, Natural Boosting and Pediatric Brain and CNS Tumor Incidences
Authors: Singh Samer , Diwakar Amita , Singh Rakesh K.
Published: April 2023

Bacille Calmette-Guérin (BCG) vaccination supposedly imparts and augments “trained immunity” that cross-protects against multiple unrelated pathogens and enhances general immune surveillance. Gradual reductions in tuberculosis burden over the last 3-5 decades have resulted in the withdrawal of BCG vaccination mandates from developed industrialized countries while reducing to a single neonatal shot in the rest. Concurrently, a steady increase in early childhood Brain and CNS (BCNS) tumors has occurred. Though immunological causes of pediatric BCNS cancer are suspected, the identification of a causal protective variable with an intervention potential has remained elusive. An examination of the countries with contrasting vaccination policies indicates significantly lower BCNS cancer incidence (per hundred-thousand) in countries following neonatal BCG inoculations (n=146)vs. non-BCG countries (n=33) [Mean: 1.26vs. 2.64; Median: 0.985vs. 2.8; IQR: 0.31–2.0vs. 2.4–3.2;P=<0.0001(two-tailed)]. Remarkably, naturalMycobacteriumspp. exposure likelihood is negatively correlated with pediatric BCNS cancer incidences in all affected countries [r(154): —0.6085,P=<0.0001]. Seemingly, neonatal BCG vaccination and natural “boosting” are associated with a 15-20-fold lower BCNS cancer incidence. We attempt to synthesize existing evidence implying the immunological basis of early childhood BCNS cancer incidences and briefly indicate possible causes that could have precluded objective analysis of the existing data in the past. A comprehensive evaluation of immune training as a potential protective variable through well-designed controlled clinical trials or registry-based studies as feasible may be warranted for its potential applications in reducing childhood BCNS cancer incidences.

Statement of Significance

Potential causal protective variable for childhood Brain and other CNS (BCNS) tumors has eluded discovery. Neonatal BCG vaccination and boosting byMycobacterium tuberculosiscomplex exposure seem associated with over 15-20 times lower BCNS cancer incidences. Data suggests neonatal BCG vaccination followed by “boosting” may be preventive for early childhood BCNS cancer incidences.
Global surveillance of novel SARS-CoV-2 variants
Authors: Patel Selina , Cumming Fergus , Mayers Carl , Charlett André , Riley Steven
Published: April 2023

Earlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance resulting in gaps in monitoring. The UK implemented large-scale community and hospital surveillance, but experience suggests it may be faster to detect new variants through testing UK arrivals for surveillance. We developed simulations of the emergence and importation of novel variants with a range of infection hospitalisation rates (IHR) to the UK. We compared time taken to detect the variant though testing arrivals at UK borders, hospital admissions, and the general community. We found that sampling 10-50% of arrivals at UK borders could confer a speed advantage of 3.5-6 weeks over existing community surveillance, and 1.5–5 weeks (depending on IHR) over hospital testing. We conclude that directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.
ReCom: A semi-supervised approach to ultra-tolerant database search for improved identification of modified peptides
Authors: Laguillo-Gómez Andrea , Calvo Enrique , Martín-Cófreces Noa , Lozano-Prieto Marta , Sánchez-Madrid Francisco , Vázquez Jesús
Published: April 2023

Open-search methods allow unbiased, high-throughput identification of post-translational modifications in proteins at an unprecedented scale. The performance of current open-search algorithms is diminished by experimental errors in the determination of the precursor peptide mass. In this work we propose a semi-supervised open search approach, called ReCom, that minimizes this effect by taking advantage of a priori known information from a reference database, such as Unimod or a database provided by the user. We present a proof-of-concept study using Comet-ReCom, an improved version of Comet-PTM. Comet-ReCom increased identification performance of Comet-PTM by 68%. This increased performance of Comet-ReCom to score the MS/MS spectrum comes in parallel with a significantly better assignation of the monoisotopic peak of the precursor peptide in the MS spectrum, even in cases of peptide coelution. Our data demonstrate that open searches using ultra-tolerant mass windows can benefit from using a semi-supervised approach that takes advantage from previous knowledge on the nature of protein modifications.

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