bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-cultural Adaptation and Validation of the Hebrew Version of the Vulvar Functional Status Questionnaire (VQ)
Authors: Tene Lea , Weintraub Adi Y. , Kalichman Leonid
Published: February 2023

Background:

As yet, no Hebrew language vulvar functional status questionnaire exists.

Aims:

To perform a cross-cultural adaptation of a Hebrew version of the Vulvar Functional Status Questionnaire (VQ), a validated tool used for evaluating dyspareunia among women, and to evaluate the psychometric properties of this version by examining the correlations between results of the questionnaire among women with pain during intercourse and quality of life, level of anxiety, and pelvic floor function.

Methods:

The English version of the VQ underwent cross-cultural adaptation to Hebrew according to accepted guidelines. Eighty Hebrew-speaking women with vulvar pain, aged older than 18 years, participated in the study. Participants completed the VQ-Hebrew (VQ-H) (see Supplemental Digital Content, available at: http://links.lww.com/JWHPT/A89), the Hebrew versions of the health-related quality-of-life questionnaire (SF-12), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12), and the State-Trait Anxiety Inventory (STAI). All the participants completed the VQ-H again after 2 to 3 weeks. Psychometric properties (test-retest reliability, internal consistency, convergent validity, and factor analysis) were calculated.

Results:

The VQ-H demonstrated excellent test-retest reliability: intraclass correlation coefficients ranged from 0.898 to 0.958 (P < .001); the Cronbach α was excellent (0.935). A significant correlation was found between the VQ-H and SF-12 scores (r =−0.360, P = .001). However, the correlation between the VQ-H and STAI and PISQ-12 scores was not statistically significant (r = 0.172, P = .127 and r =−0.185, P = .100, respectively). Factor analysis revealed a 4-factor solution representing daily function and pain provoked by or related to various activities.

Conclusion:

The VQ-H is a valid and reliable instrument. Its scores reflect the impaired function in all domains of vulvar pain among Hebrew-speaking women.
Addressing the Kinetic Chain in a Postpartum Multisport Athlete: A Case Report
Authors: Piropato Lisa , Deering Rita
Published: February 2023

Background:

Physiological and biomechanical changes must be considered when evaluating and treating musculoskeletal impairments in a perinatal female athlete, whether or not these impairments are directly related to their pregnant or postpartum state.

Case Description:

This case report describes a 34-year-old woman active in high-intensity functional conditioning, recreational volleyball, and running, seeking care for shoulder and thoracic back pain from birth to 1 year postpartum. Her primary complaint of shoulder pain was exacerbated by overhead activities. She also presented with a secondary complaint of “weakness” through her core, preventing return to sport. Treatment focused on joint mobilizations, neuromuscular re-education, and core strength using biotensegrity principles throughout the postpartum journey of return to sport.

Outcomes:

The patient was highly motivated and met her desired goals to (1) compete in recreational sand and indoor volleyball starting at 6 weeks postpartum, (2) participate in a relay trail race at desired pace, and (3) compete in a weightlifting competition at 8 months postpartum without an increase in shoulder pain.

Discussion:

This case demonstrates the importance of addressing the entire kinetic chain in the postpartum athlete while addressing what may be considered a “straightforward” orthopedic condition. Understanding birth and postpartum healing is essential for physical therapists working with active mothers. Knowledge of the physiological and biomechanical changes during and after pregnancy is essential to appropriate treatment of these patients.

Informed Consent:

Written consent was obtained.
Physician assistant and nurse practitioner onboarding in primary care: The participant perspective
Authors: Ortiz Pate Nathalie , Barnes Hilary , Batchelder Heather , Anglin Lorraine , Sanchez Mara , Everett Christine , Morgan Perri
Published: February 2023

Background:

Many new graduate primary care physician assistants (PAs) and nurse practitioners (NPs) can experience stress and difficulty as they transition to practice. Feelings of anxiety and role ambiguity are common and can lead to costly turnover, impact care continuity, and place patients at risk for poor clinical outcomes. Onboarding, the process of helping new hires adjust to social and performance aspects of their new job and has the potential to ease transition to practice for PAs and NPs. Recent research has linked PA/NP onboarding programs to increased engagement, decreased turnover, and higher clinical productivity.

Purpose:

To describe new graduate PA and NP perspectives of onboarding programs they completed in their first primary care position.

Methodology:

Thirteen semistructured interviews were conducted with new graduate PAs and NPs who participated in onboarding programs. Interviews were transcribed and then analyzed using an inductive coding methodology.

Results:

Analyses revealed nine thematic concepts that are described within two frameworks. Structural components include improving competence, training on the electronic health record, promoting mentorship, orienting to organizational dynamics, tailoring ramp-up of patient scheduling, clarifying expectations, and providing clear organizational support. Psychosocial factors include creating comfort and building self-confidence.

Conclusion:

Understanding participants' experiences with onboarding programs is essential for ensuring successful transition to practice for new graduate PAs and NPs.

Implications:

These findings are beneficial to the health care workforce. Administrators can incorporate these findings into existing and future programs, and new graduate PAs and NPs can negotiate for the inclusion of these components in their first position.
Impact of different ischemia times on biliary stricture after living donor liver transplantation with biliary atresia
Authors: Zhao Shengqiao , Zhang Zhixin , Si Zhuyuan , Dong Chong , Sun Chao , Wang Kai , Zhang Wei , Zheng Weiping , Wei Xinzhe , Gao Wei , Shen Zhongyang
Published: February 2023

Biliary atresia (BA) is the most common indication for pediatric liver transplantation, and biliary stricture (BS) remains an Achilles’ heel for pediatric living donor liver transplantation (LDLT). We investigated the impact of different ischemia times on BS after LDLT in patients with BA. We retrospectively analyzed patients (<18 y) with BA who underwent LDLT between January 2016 and December 2020. Cases with hepatic artery thrombosis, bile leakage, early BS (<2 wk), and early death (<3 mo) were excluded. In all, 572 cases were included. A total of 26 cases (4.55%, 26/572) developed BS: 25 patients with anastomotic stricture and 1 patient with anastomotic stricture combined with left hepatic duct stricture. In addition, the time to diagnosis of BS ranged from 1.8 to 53.0 months (mean, 13.0 mo and median, 8.2 mo) after transplantation. A multivariate logistic regression analysis showed that arterial ischemia time (AIT), per 10 minutes (OR=1.222, 95% CI: 1.007–1.438, p=0.04) was the only independent risk factor for the development of BS after LDLT in patients with BA. What is more, the 5-year cumulative risk of BS between the AIT ≥40 minutes and AIT <40 minutes groups was 2.79% versus 10.57%. AIT was the only independent risk factor for the development of BS after LDLT with BA, and AIT ≥40 minutes would increase the 5-year cumulative risk of BS in our study. A shorter AIT, especially AIT <40 minutes, should be kept to decrease BS.
Neurological infection and complications of SARS-CoV-2: A review
Authors: Singh Santosh , Meher Nikita , Mohammed Arifullah , Razab Mohammad Khairul Azhar Abdul , Bhaskar L.V.K.S. , Nawi Norazlina Mat
Published: February 2023

The primary target of severe acute respiratory syndrome coronavirus 2 is the respiratory system including the nose and lungs, however, it can also damage the kidneys, cardiovascular system and gastrointestinal system. Many recent reports suggested that severe acute respiratory syndrome coronavirus 2 infections can also affect the central nervous system as well as peripheral nervous system that lead to the several neurological complications. The virus can break the blood brain barrier and enters the brain via haematological route or directly by the angiotensin-converting enzyme 2 receptors present on endothelial cells of many cerebral tissues. The neurological complications are manifested by headache, dizziness, encephalopathy, encephalitis, cerebrovascular disease, anosmia, hypogeusia, muscle damage, etc. This review article described the possible routes and mechanism of nervous system infection and the range of neurological complications of COVID-19 that may help the medical practitioners and researchers to improve the clinical treatment and reduce the mortality rate among patients with viral diseases.
Subcutaneous stretching enlarges adjacent vertebral artery instantly in patients with cervicogenic dizziness: Two case reports
Authors: He Qingtao , Huang Huiyi , Liang Hongyu , Chou Li-Wei , Fu Zhonghua
Published: February 2023

Rationale:

Fu's subcutaneous needling (FSN) is effective for cervicogenic dizziness (CGD), which is often a result of vascular problems. Here, we attribute the positive treatment effect of FSN for CGD to improvements in vascular problems.

Patient concern:

Two patients were experiencing low quality of life due to reproducible dizziness.

Diagnosis:

Two patients with cervical spine disorder, presented with neck pain and reproducible dizziness. Other causes of dizziness were excluded.

Interventions:

Case 1 received 1 session of FSN treatment, while case 2 received 3 sessions of FSN treatment in a month.

Outcomes:

The dizziness and neck pain experienced by both patients instantly improved significantly after FSN treatment, and the luminal diameter of the vertebral artery (VA) measured by carotid and VA ultrasound enlarged simultaneously up to 1.29-fold and 1.09-fold for both cases. According to the Hagen–Poiseuille equation, the blood flow volume increased 2.77-fold and 1.43-fold, respectively. Case 2 recovered from CGD with 1.19-fold VA luminal diameter increment and about 2.01-fold increase of blood flow volume in a month.

Lessons:

Subcutaneous stretching provides a safe, convenient and immediate solution to CGD, and supports the diagnosis and treatment of CGD under carotid and VA ultrasound. This study suggests that stretching subcutaneously can influence adjacent VA, which may also help improve some cerebrovascular diseases.
Systematic review and meta-analysis of reflexology for people with multiple sclerosis: Systematic Review and Meta-Analysis
Authors: Ma Xiaohong , Yuan Zhaoyu , Qian Baicheng , Guan Yunxiang , Wang Baoliang
Published: February 2023

Background:

Research on reflexology therapy for multiple sclerosis (MS) is limited, and the evaluation is mixed. Our aim is to confirm the efficacy of reflexology therapy for MS.

Methods:

The preferred reporting items for systematic reviews and meta-analyses guidelines were followed. The search strategy was conducted in PubMed, Embase, the Cochrane Library, and the Science Citation Index. The quality of the included trials was assessed by the Cochrane Handbook. The main results were summarized and analyzed in RevMan 5.4.

Results:

A total of 11 studies were included in the final analysis. There were significant differences [mean difference (MD) –0.90, 95% confidence interval (CI) –1.37 to –0.43, heterogeneity I
2 = 0%] between the Precision Reflexology and Sham Reflexology groups in visual analogue scale pain. There was a significant difference (MD –1.00, 95% CI –1.42 to –0.58, heterogeneity I
2 = 93%) between the Precision Reflexology and Sham Reflexology groups on the fatigue severity scale. There was no difference between the Precision Reflexology and Sham Reflexology groups in physical function (MD 6.88, 95% CI –3.36 to 17.13, heterogeneity I
2 = 31%), role disorder due to physical problems (MD 10.20, 95% CI –4.91 to 25.30, heterogeneity I
2 = 0%), physical pain (MD 7.68, 95% CI –0.09 to 15.45, heterogeneity I
2 = 0%), role disorder due to emotional problems (MD 3.41, 95% CI –11.55 to 18.37, heterogeneity I
2 = 0%), energy (MD 3.27, 95% CI –4.32 to 10.87, heterogeneity I
2 = 0%), emotional well-being (MD 1.79, 95% CI –4.76 to 8.34, heterogeneity I
2 = 0%), social function (MD 5.72, 95% CI –3.48 to 14.91, heterogeneity I
2 = 0%), or general health (MD 2.63, 95% CI –4.36 to 9.62, heterogeneity I
2 = 0%).

Conclusions:

Reflexology therapy can be used as an effective intervention for the pain and fatigue of MS patients while improving the quality of life.
The risk of ischemic cerebrovascular disease associated with benzbromarone use in gout people: A retrospective cohort study in Taiwan
Authors: Lai Shih-Wei , Liao Kuan-Fu , Kuo Yu-Hung , Hwang Bing-Fang , Liu Chiu-Shong
Published: February 2023

Epidemiological studies have shown that people having hyperuricemia are at increased risk of ischemic cerebrovascular disease. This research aimed to study the relation of ischemic cerebrovascular disease with benzbromarone use among persons with gout-related disorders. This was a retrospective cohort design utilizing a 2003 to 2015 national health insurance database in Taiwan. Subjects aged 20 to 99 years who already had suffered from gout-related disorders were included as eligible subjects. Eligible persons who had the benzbromarone prescription alone were selected into the benzbromarone group. Sex-matched and age-matched eligible persons who never used any urate-lowering agents were selected into the control group. An index date was set as a date of benzbromarone being prescribed. The end-point was defined as ischemic cerebrovascular disease being newly diagnosed. A hazard ratio was applied to measure the association strength between benzbromarone use and ischemic cerebrovascular disease. Totally, there were 13,398 persons in the benzbromarone group and 13,398 persons in the control group. The incidence rate of ischemic cerebrovascular disease seemed to be modestly higher in the benzbromarone group than the control group, but it did not achieve statistical significance (0.78 vs 0.75 every 100 person-years, incidence rate ratio = 1.05, 95% confidence interval = 0.94–1.16). A crude hazard ratio of ischemic cerebrovascular disease showed 1.05 in the benzbromarone group (95% confidence interval = 0.94–1.17, P = .373) comparing with the control group. No significant association can be detected between benzbromarone use and the probability of ischemic cerebrovascular disease among persons with gout-related disorders. We think that reduction of the serum uric acid by use of benzbromarone could not be related to the probability of ischemic cerebrovascular disease. Further research is suggested to clarify this issue.
Metronidazole-induced encephalopathy delayed diagnosis due to cerebellar infarction: A case report
Authors: Cha Sangha , Lee Byung Chan , Moon Chang-Won , Cho Kang Hee
Published: February 2023

Rationale:

Metronidazole is a 5-nitroimidazole antibiotic effective against anaerobic bacterial and parasitic infections. Long-term use may cause side effects in the central nervous system, although the occurrence of encephalopathy is rare.

Patient concerns:

A 73-year-old man was diagnosed with acute pyelonephritis and received antibiotic treatment. During the treatment, the patient complained of back pain. Lumbar spinal magnetic resonance imaging (MRI) revealed infective spondylitis, and metronidazole (1.5 g) was administered daily for approximately 160 days. The patient developed cognitive dysfunction and gait disorder after antibiotic treatment, and brain MRI showed acute infarction in both cerebellar lobes. Secondary prevention with antiplatelet and physiotherapy was prescribed; however, functional recovery was not achieved.

Diagnosis:

After 1 month, a follow-up brain MRI showed high signal intensity and diffusion restriction in the corpus callosum on diffusion-weighted images and high signal intensity in the dentate nucleus on T2-weighted images. Therefore, metronidazole-induced encephalopathy was suspected.

Interventions:

Metronidazole was discontinued, and ceftriaxone (2 g/day) was administered to manage the infective spondylitis.

Outcomes:

One week after the discontinuation of the drug, the patient’s cognition improved to the extent that communication was possible. Thus, even if other neurological deficits, such as cerebellar infarction, are found in patients with long-term disability, the possibility of metronidazole-induced encephalopathy should be considered when metronidazole is used for a long time.
Using temporal heatmaps to identify worthwhile articles on immune checkpoint blockade for melanoma (ICBM) in Mainland China, Hong Kong, and Taiwan since 2000: A bibliometric analysis
Authors: Juang Shiow-Jen , Lin Cheng-Yao , Chien Tsair-Wei , Chou Willy , Lai Feng-Jie
Published: February 2023

Background:

Melanoma is a life-threatening form of skin cancer. Due to its remarkable effectiveness, the immune checkpoint blockade is widely used to treat melanoma (ICBM). No research has been conducted on ICBM for identifying the most readable articles. A bibliometric analysis of 100 top-cited ICBM (T100ICBM) in recent decades is required to highlight articles worth reading.

Methods:

Based on the Web of Science Core Collection, we summarized the articles on ICBM published in each year from 2000 to 2022, with first authors from Mainland China, Hong Kong, and Taiwan (CHT). Using the CJAL score, data extraction and visualization of the distribution of ICBM publications were conducted on 2718, and 100 top-cited articles, respectively. We used the temporal heatmap to identify the most readable articles. Four descriptive, diagnostic, predictive, and prescriptive analytics (called DDPP model) were applied to describe the features of T100ICBM articles. The absolute advantage coefficient was used to determine the dominance extent of the most influential region, institute, department, and author.

Results:

A total of 2718 publications was included after removing first or corresponding authors who were not affiliated with CHT. Publications by year showed a sharp increase from 2014 onward and either peaked in 2022 or have not yet peaked. It was evident that there was a large difference between the number of publications in provinces/metropolitan cities/regions on CHT. Beijing, Sichuan University, Oncology, and Guo Jun from Beijing are the most prolific and influential region, institute, department, and author. When comparing research achievements to the next productive authors based on the CJAL score, only Dr Jun has a medium effect of dominance (=0.60). On the basis of their consecutive growth in citations over the past 4 years, 20 T100ICBM articles were recommended for readers.

Conclusion:

The field of ICBM is growing rapidly, and Beijing and Sichuan University are taking the lead in CHT. Furthermore, the study provides references for worth-reading articles using the temporal heatmap. Future research hot spots may focus on these 4 themes of immunotherapy, melanoma, metastatic melanoma, regulatory T cells, cells, and activation, which may pave the way for additional study.
Hernia uterine inguinale associated with Mayer-Rokitansky-Küster-Hauser syndrome: Three case reports and literature review
Authors: Dai Yifei , Qin Chenglu , Zhu Linling , Luo Guangnan
Published: February 2023

Rationale:

Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome) present with genital inguinal hernia was rare and probably under reported, on account of lack in typical gynecological symptom. It should be regarded with care.Here 3 cases diagnosed at our institution with detailed clinical information were present, and the literature was reviewed to paint a comprehensive profile of hernia uterine inguinale associated with MRKH syndrome.

Patient concerns:

Case no. 1 was a 36-year-old female with recurrent dragalgia for 5 years. Left rudimentary uterus at the left groin area was revealed by sonography scan and confirmed by diagnostic laparoscopy.Case no. 2 was a 27-year-old woman diagnosed with MRKH syndrome and her MRI examination suggested a suspicious swelling measuring 2.0cm×2.0cm in left groin. The left nonfunctionally rudimentary uterus and adnexa were incarcerated in the left inguinal hernial sac, which was revealed by laparoscopy.Case no. 3 was a 29-year-old woman, admitted with right abdominal pain with a provisional diagnosis of appendicitis. After appendicectomy, pelvic exploration showed a part of left rudimentary uterus and elongated oviduct herniated through the left internal inguinal ring.

Diagnoses:

Hernia uterine inguinale associated with MRKH syndrome.

Interventions and outcomes:

Case no.1: When the rudimentary uterus was pulled out from the hernia sac, it appearance dark ocher. Then the left rudimentary uterus was removed and the indirect defect of inguinal duct was closed.The patient was followed up for 18 months with no recurrence of abdominal pain.Case no.2 and 3:The left rudimentary uterus were replaced from the hernia sac, and the indirect defect was fixed with sutures.The patients recovered smoothly without complications for 12-month follow-up.

Lessons:

Left involvement of rudimentary uterus was frequently observed in patients with MRKH syndrome, along with ipsilateral ovary and/or fallopian tube horned in the hernia. Abdominal pain or inguinale mass could be the chief complaints while some individuals were asymptomatic. Either surgical removal or replacement of rudimentary uterus was an effectively optional treatment strategy for hernia uterine inguinale.When a patient with MRKH syndrome presented with abdominal pain of unknown cause or inguinal mass, rudimentary uterine inguinal hernia should be suspected.
Hepatic artery pseudoaneurysm caused by chronic pancreatitis: Case report and literature review
Authors: Jia Fengjuan , Xia Guodong , Zhu Qingliang , Yu Shuangyu , Hu Nan , Zhang Hailong
Published: February 2023

Rationale:

Visceral artery pseudoaneurysm is a rare complication of chronic pancreatitis (CP), all pancreatic or peripancreatic arteries have been reported to be involved, while hepatic artery is less common.

Patient concerns:

This case report illustrated a 42-year-old man with CP who developed right hepatic artery pseudoaneurysm (HAP), and finally he was treated with intravascular embolization.

Diagnoses:

The patient suffered from HAP due to acute attack of CP.

Interventions:

The pseudoaneurysm located in a fine branch of right hepatic artery was embolized.

Outcomes:

The HAP of the patient was cured. He had no recurrent bloody stool or abdominal pain. The symptoms gradually relieved.

Conclusion:

Herein, we report a patient with CP who developed right HAP causing infected hematoma, gastrointestinal bleeding, and obstructive jaundice, and a literature review is also presented. HAP caused by CP is a rare disease in the clinic, but rupture of pseudoaneurysm is fatal. Careful evaluation, early detection, and prompt treatment should be performed when the patient is admitted and followed up.
Weekly paclitaxel treatment in the first-line therapy of classic Kaposi sarcoma: A real-life study
Authors: Paksoy Nail , Khanmammadov Nijat , Doğan İzzet , Ferhatoğlu Ferhat , Ahmed Melin Aydan , Karaman Sule , Aydiner Adnan
Published: February 2023

Kaposi sarcoma is an angioproliferative disease associated with human herpes virus 8 infection. Classic Kaposi sarcoma (CKS) usually develops in older age. Although CKS often does not require systemic therapy, systemic therapy can be administered in progressively symptomatic patients. In this real-life study, we purposed to determine effectiveness and safety of weekly paclitaxel therapy in the first-line treatment of CKS. In this cross-sectional retrospective study, we analyzed the clinical data of 44 patients with CKS who received first-line paclitaxel therapy between January 2000 and December 2020. Paclitaxel was administered by intravenous infusion 80 to 100 mg/weekly. The median age of the patients was 67 years (range, 39–86 years), and majority male (77.2%). All patients had cutaneous involvement in extremities. The median follow-up time from paclitaxel treatment was 39.1 (range, 3.7–173.5) months. The median progression free survival from start of therapy was 35.1 months (range, 2–144 months). Complete response, partial response and stable disease were observed in 7 (15.9%), 28 (63.7%) and 6 (13.6) patients, respectively. Objective control rate was 79.6%, and the median response time after the last dose of paclitaxel was 18.2 months. A total of 4 patients (9.1%) had grade 3 to 4 neutropenia, but it was not complicated by febrile neutropenia. Three patients (6.8%) experienced grade 3 to 4 peripheral neuropathy. No patient had grade 3 to 4 allergic reaction. There was no drug-related death. According to our results, paclitaxel is an effective therapy option with an acceptable safety profile for patients with advanced CKS.
Implementing a Specifications Grading System in a Nursing Course
Authors: Dabney Beverly W. , VanDerWoude Carissa J.
Published: February 2023

Background:

Nurse educators are charged with the challenging task of evaluating student learning and abilities effectively using traditional student assessment methods, which come with several inherent shortcomings. New guidelines for nurse educators now present a more competency-based approach to nursing education that calls for objective-driven assessments.

Problem:

Traditional grading practices lack the ability to connect student learning to their final course grades. However, specifications grading, which directly links grades to learning objectives, has not been not adequately explored in the nursing literature.

Approach:

A specifications grading system was designed and implemented in an online undergraduate nursing research course. Student and faculty feedback on the system were reviewed.

Conclusions:

Overall, students and faculty approved of the specifications grading system. Recommendations are presented for adopting specifications grading in nursing courses. Research is needed to explore student perceptions of the grading system and its effects on student learning and performance.
Comparison of Computer-Assisted Self-Interview Versus Clinician Interview for Self-Reported Vulvovaginal Symptoms
Authors: Robbins Sarah J. , Brown Sarah E. , Stennett Christina A. , Tuddenham Susan , Johnston Elizabeth D. , He Xin , Mark Katrina S. , Brotman Rebecca M.
Published: February 2023

This secondary analysis (N = 43) compared computer-assisted self-interview (CASI) to clinician interview for self-report of 8 vulvovaginal symptoms. Concordance was moderate between interview modes (range, 70–86%) with itching and odor having highest agreement. Although prior reports suggest more responses on CASI, we found CASI did not significantly increase self-report of symptoms over clinician interview.
Health Care Provider Decisions to Initiate Oral HIV Preexposure Prophylaxis in New York City Public Sexual Health Clinics
Authors: Hoffman Susie , Jamison Kelly , Pathela Preeti , Gonzalez-Argoti Tatiana , Rivera Angelic , Leu Cheng-Shiun , Hubbard Stephanie , Castro Michael , Borges Christine , Gandhi Anisha , Edelstein Zoe , Myers Julie , Mantell Joanne E. , Bauman Laurie J.
Published: February 2023

Background

Oral HIV preexposure prophylaxis (PrEP) is safe and effective but underutilized. Health care providers' beliefs about PrEP and attitudes toward people who could benefit may affect PrEP access.

Methods

This mixed-methods study (2016–2018) was conducted in 8 New York City public sexual health clinics that implemented a PrEP program. Data included 32 in-depth qualitative interviews with clinicians, quantitatively coded to reflect their PrEP beliefs; a provider questionnaire; and 6 months of medical record visit data for these providers. Among patients with a PrEP indication, we examined the odds of a patient being initiated on PrEP associated with providers' PrEP beliefs and demographic characteristics, and patient characteristics.

Results

Providers reported strong support for offering PrEP to eligible patients. The majority denied concerns about possible development of drug-resistant viral strains, giving PrEP to people who might not benefit, and PrEP toxicity. Nevertheless, about one-third agreed with each of these concerns, and 55% thought PrEP use might limit condom use. Of 2176 patients with a PrEP indication, 20% were initiated. Providers with more restrictive PrEP beliefs did not have lower odds of initiating patients on PrEP. Women as well as Black and Latinx patients were less likely to be initiated on PrEP.

Conclusions

Contrary to our hypotheses, providers' negative PrEP beliefs did not seem to reduce initiation of PrEP for eligible patients. This may be attributable to clear clinical protocols, strong staff support, and training on implementing PrEP in this setting. Racial and gender disparities in PrEP uptake urgently require attention.
Bias assessment and correction for Levin’s population attributable fraction in the presence of confounding
Authors: Ferguson John , Alvarez Alberto , Mulligan Martin , Judge Conor , O’Donnell Martin
Published: February 2023

In 1953, Morton Levin introduced a simple approach to estimating population attributable fractions (PAF) depending only on risk factor prevalence and relative risk. This formula and its extensions are still in widespread use today, particularly to estimate PAF in populations where individual data is unavailable. Unfortunately, Levin’s approach is known to be asymptotically biased for the PAF when the risk factor-disease relationship is confounded even if relative risks that are correctly adjusted for confounding are used in the estimator.

An alternative estimator, first introduced by Miettinen in 1972, is unbiased for the PAF provided the true relative risk is invariant across confounder strata. However, despite its statistical superiority, Miettinen’s estimator is seldom used in practice, as its direct application requires an estimate of risk factor prevalence within disease cases rather than an estimate of risk factor prevalence in the general population.

Here we describe a simple re-expression of Miettinen’s estimand that depends on the causal relative risk, the unadjusted relative risk and the population risk factor prevalence. While this re-expression is not new, it has been underappreciated in the literature, and the associated estimator may be useful in estimating PAF in populations when individual data is unavailable provided estimated adjusted and unadjusted relative risks can be transported to the population of interest. Using the re-expressed estimand, we develop novel analytic formulae for the relative and absolute asymptotic bias in Levin’s formula, solidifying earlier work by Darrow and Steenland that used simulations to investigate this bias. We extend all results to settings with non-binary valued risk factors and continuous exposures and discuss the utility of these results in estimating PAF in practice.
Epoxyeicosatrienoic acids and sEH inhibition prevent cardiac dysfunction in CVB3-induced myocarditis by positively regulating type I interferon signaling
Authors: Zhou Zhou , Zhang Min , Zhao Chengcheng , Gao Xu , Wen Zheng , Wu Junfang , Chen Chen , Hu Jiong , Fleming Ingrid , Wang Dao Wen
Published: February 2023

Myocarditis is a challenging inflammatory disease of the heart and better understanding of its etiology is needed to develop specific drug therapies. Epoxyeicosatrienoic acids (EETs), active molecules synthesized by cytochrome P450 enzymes from arachidonic acids and hydrolyzed to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), have been attributed anti-inflammatory activity. Here, we investigated whether EETs have immunomodulatory activity and exert protective effects on coxsackie B3 virus (CVB3)-induced myocarditis. Viral infection altered eicosanoid epoxide and diol levels in both patients with myocarditis and, in the murine heart, and correlated with the increased expression and activity of the sEH after CVB3 infection. Administration of a sEH inhibitor prevented CVB3-induced cardiac dysfunction and inflammatory infiltration. Importantly, EET/sEH inhibitor treatment attenuated vial infection/ improved viral resistance by activating type I interferon (IFN) signaling. At the molecular level, EETs enhanced the interaction between glycogen synthase kinase 3β (GSK3β) and TANK-binding kinase 1 (TBK1) to promote IFN-β production. Our findings revealed that EETs and sEH inhibitors prevent the progress of CVB3-induced myocarditis, particularly by promoting viral resistance by increasing IFN production.
Algorithmic Virtual Reality Reduces Parkinsonian Tremor
Authors: Cornacchioli John , Galambos Alec , Rentouli Stamatina , Canciello Robert , Marongiu Roberta , Cabrera Daniel , Njie eMalick G.
Published: February 2023

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders, affecting approximately 6-7 million patients worldwide. Involuntary hand tremor (IHT), one of the cardinal motor symptoms of PD, is extremely debilitating to patients reducing their quality of life. In this study, we combined neuroscience together with the nascent field of medical virtual reality (VR). Our goals were to 1) generate technology to enable PD patients to leapfrog the real life difficulties of living with IHT by entering VR metaverse worlds in which they are tremor-free and can function at new heights, 2) to determine whether lack of tremors in VR modifies central biofeedback mechanisms to non-invasively reduce tremors in real life. We thus generated algorithms that adjusted the moving average centroid of digital hands to stabilize tremors in VR. We implemented these algorithms in the Oculus Rift VR system and enrolled nine subjects with PD in a trial that yielded several important observations. First, we established the Oculus Rift as a potent measurement device for IHT. Secondly, we determined parkinsonian tremors can be abolished in VR with algorithms that removed up to 99% of tremors from PD subjects’ digital hands (76% average reduction). These data suggest PD subjects can enter VR and be asymptomatic of PD IHT. To test whether our algorithms have measurable practical utility, we created a VR painting application, FingerPaint, and tested it against TiltBrush the leading VR painting application. We empirically demonstrate that complex freeform art created in FingerPaint had up to 51% reduction in tremor-associated parkinsonian drawing irregularities (24% average reduction). Lastly, we generated a technical framework wherein movements in the real-world can be measured side-by-side with those in VR. With this framework, we observed real life parkinsonian tremors were significantly reduced by up to 87% in real life when our algorithms abolished digital hand tremors in VR (35% average reduction). This reduction was observed in 78% of subjects and was progressive as subjects had increasingly reduced real life tremors the longer they were in VR.
Bioinformatic analysis of the spike protein cleavage sites of coronaviruses in the mammalian order Eulipotyphla
Authors: Guo Qinghua , Choi Annette , Millet Jean K. , Whittaker Gary R.
Published: February 2023

The mammalian order Eulipotyphla, including hedgehogs and shrews, represent a poorly understood reservoir of coronaviruses with zoonotic potential. Here, we carried out a bioinformatic analyses of these viruses based on the viral spike protein—to illustrate the complexity of coronavirus evolutionary history and the diversity of viruses from these host species, with a focus on the presence of possible furin cleavage sites within the spike protein. We found no evidence for cleavage by furin itself; however, certain strains of Wencheng Sm Shrew coronavirus were shown to have a predicted cleavage site for other member of the proprotein convertases, which are furin family members— suggesting their spillover potential. As the expanding urbanization and the trade of small mammals in the wet markets enhance the wildlife-human interactions, this may increase pathogen spillover risks. Therefore, we should implement broad wild animal surveillance and be vigilant of contact with these small wild mammals in light of one-health perspectives.
DLKcat cannot predict meaningfulkcatvalues for mutants and unfamiliar enzymes
Authors: Kroll Alexander , Lercher Martin J.
Published: February 2023

The recently published DLKcat model, a deep learning approach for predicting enzyme turnover numbers (kcat), claims to enable high-throughput kcat predictions for metabolic enzymes from any organism and to capturekcatchanges for mutated enzymes. Here, we critically evaluate these claims. We show that DLKcat predictions become positively misleading for enzymes with less than 60% sequence identity to the training data, performing worse than simply assuming a meankcatvalue for all reactions. Furthermore, DLKcat’s ability to predict mutation effects is much weaker than implied, capturing only 3% of the experimentally observed variation across mutants not included in the training data. These findings highlight significant limitations in DLKcat’s generalizability and its practical utility for predictingkcatvalues for novel enzyme families or mutants, which are crucial applications in fields such as metabolic modeling.
Body size-dependent effects on the distribution patterns of phoretic mites of the multi-symbiontRhynchophorus ferrugineus(Olivier, 1790) host
Authors: Matos Inês , Silva Diogo , Oliveira João , Gonçalves Claúdia , Alves Rita , Pereira Nuno , Catarino Francisco , Ameixa Olga M. C. C. , Sousa José Américo , Rangel Luis Filipe , Santos Maria João , Ayra-Pardo Camilo
Published: February 2023

Phoretic mites have been found attached to different body parts of the red palm weevil (RPW),Rhynchophorus ferrugineus(Olivier, 1790), to disperse. However, the question of how the patterns of attachment sites are formed remains intriguing. Here, we conducted the first study of RPW-associated phoretic mites in Portugal, particularly in the districts of Viana do Castelo, Braga, Porto and Aveiro in Northern Portugal (macrohabitat), and investigated the patterns of mite distribution on six body parts of RPW (microhabitat). At the macrohabitat level, we detected seven phoretic mite taxa actively using the RPW host in each of the four studied districts, all documented for the first time in association with this invasive exotic species in Portugal. However, their relative abundance (species evenness) varied between districts, as did species diversity. All examined weevils carried mites, and the prevalence of the different taxa did not differ between districts or sex of weevils. Measured by mean abundance and degree of aggregation,Centrouropodasp. proved to be the common dominant taxon, whileAcarussp. AndC. rhynchoporuswere considered common subordinate taxa andUroovobellasp., Mesostigmata,N. extremicaandDendrolaelapssp. sparse taxa. At the microhabitat level, all taxa were present in all body parts of the RPW; the highest abundance was in a region encompassing the inner surface of the elytra and the membranous hind wings (subelytral space). Analysis of niche overlap revealed that the distribution patterns of phoretic mite taxa on the RPW were not randomly structured. In the subelytral space, interspecific coexistence of mites increased as a function of body size difference with the dominantCentrouropodasp. We conclude that the distribution patterns of RPW-associated phoretic mites show body size-dependent effects that resulted in the dominant taxon displacing similar size taxa and accepting taxa with which it has the greatest size difference as co-habitants.
Flexible visual learning and memory in nectar foraging hornets
Authors: Lacombrade Mathilde , Bajo Monica Doblas , Rocher Naïs , Navarro Emmanuel , Lubat Christian , Vogelweith Fanny , Thiéry Denis , Lihoreau Mathieu
Published: February 2023

Pollinators, such as bees, develop flexible memories of colours, patterns and shapes, for efficient flower recognition. Here we tested whether other insects facing the same foraging problem have evolved similar cognitive abilities for flexible learning. We trained wild hornets from two species commonly found in Europe (Vespa velutina nigrithoraxandVespa crabro) to associate sucrose solution rewards to colour stimuli in a Y maze. Hornets of both species succeeded in differential and reversal learning, and developed short and long-term memories of the learnt associations. Thus, just like bees, hornet foragers can learn various visual cue-reward associations and remember them over several hours or days for selecting flowers. Our study in non-model species illustrates how standard conditioning approaches can be used to explore and compare the cognitive abilities of animals with similar foraging ecology.
Comparative Transcriptomics and Genomics from Continuous Axenic Media Growth IdentifiesCoxiella burnetiiIntracellular Survival Strategies
Authors: Yadav Archana , Brewer Melissa N. , Elshahed Mostafa S. , Shaw Edward I.
Published: February 2023

Coxiella burnetii(Cb) is an obligate intracellular pathogen in nature and the causative agent of acute Q fever as well as chronic diseases. In an effort to identify genes and proteins crucial to their normal intracellular growth lifestyle, we applied a “Reverse evolution” approach where the avirulent Nine Mile Phase II strain of Cb was grown for 67 passages in chemically defined ACCM-D media and gene expression patterns and genome integrity from various passages was compared to passage number one following intracellular growth. Transcriptomic analysis identified a marked downregulation of the structural components of the type 4B secretion system (T4BSS), the general secretory (sec) pathway, as well as 14 out of 118 previously identified genes encoding effector proteins. Additional downregulated pathogenicity determinants genes included several chaperones, LPS, and peptidoglycan biosynthesis. A general marked downregulation of central metabolic pathways was also observed, which was balanced by a marked upregulation of genes encoding transporters. This pattern reflected the richness of the media and diminishing anabolic and ATP-generation needs. Finally, genomic sequencing and comparative genomic analysis demonstrated an extremely low level of mutation across passages, despite the observed Cb gene expression changes following acclimation to axenic media.
H3K27me3 dictates atypical genome-nuclear lamina interactions and allelic asymmetry during early embryogenesis
Authors: Guerreiro Isabel , Rang Franka J. , Kawamura Yumiko K. , Groenveld Femke C. , Beek Ramada E. van , Lochs Silke J. A. , Boele Ellen , Peters Antoine H. M. F. , Kind Jop
Published: February 2023

The very first days of mammalian embryonic development are accompanied by epigenetic reprogramming and extensive changes in nuclear organization. In particular, genomic regions located at the periphery of the nucleus, termed lamina-associated domains (LADs), undergo major rearrangements after fertilization. However, the role of LADs in regulating gene expression as well as the interplay with various chromatin marks during preimplantation development remains elusive. In this study, we obtained single-cell LAD profiles coupled with the corresponding gene expression readout throughout the first days of mouse development. We detect extensive cell-cell LAD variability at the 2-cell stage, which surprisingly does not seem to functionally affect gene expression. This suggests an unusual uncoupling between 3D-nuclear genome organization and gene expression during totipotent developmental stages. By analyzing LAD dynamics and chromatin states across early developmental stages in an allelic-specific manner, we identify genomic regions that transiently detach from the nuclear lamina and are enriched by non-canonical H3K27me3. Upon maternal knock-out of a component of the Polycomb repressive complex 2 and concomitant loss of H3K27me3 during early embryogenesis, these regions relocate to the lamina at the 2-cell stage. Our results suggest that H3K27me3 is the prime determinant in establishing the atypical distribution of the genome at the nuclear periphery during the first days of embryonic development. This study provides insight into the molecular mechanisms regulating nuclear organization of parental genomes during very early mammalian development.
A deep-learning driven investigation of circuit basis for reflexive hypersensitivity to pain
Authors: Reddy Prannay , Vasudeva Jayesh , Shah Devanshi , Prajapati Jagat Narayan , Harikumar Nikhila , Barik Arnab
Published: February 2023

Objectively measuring animal behavior is key to understanding the neural circuits underlying pain. Recent progress in machine vision has presented us with unprecedented scope in behavioral analysis. Here, we apply DeeplabCut (DLC) to dissect mouse behavior on the thermal-plate test — a commonly used paradigm to ascertain supraspinal contributions to noxious thermal sensation and pain hypersensitivity. We determine the signature characteristics of the pattern of mouse movement and posture in 3D in response to a range of temperatures from innocuous to noxious on the thermal-plate test. Next, we test how acute chemical and chronic inflammatory injuries sensitize mouse behaviors. Repeated exposure to noxious temperatures on the thermal-plate can induce learning, and in this study, we design a novel assay and formulate an analytical pipeline that will facilitate the dissection of plasticity mechanisms in pain circuits in the brain. Last, we record and test how activating Tacr1 expressing PBN neurons — a population responsive to sustained noxious stimuli-affects mouse behavior on the thermal plate test. Taken together, we demonstrate that by tracking a single body part of a mouse, we can reveal the behavioral signatures of mice exposed to noxious surface temperatures, report the alterations of the same when injured, and determine if a molecularly and anatomically defined pain responsive circuit plays a role in the reflexive hypersensitivity to thermal pain.
Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands
Authors: Lee Hye Kyung , Willi Michaela , Liu Chengyu , Hennighausen Lothar
Published: February 2023

Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication1and contains eight genes and 20 candidate regulatory elements, including a super-enhancer. Five genes are expressed in mammary glands and account for 50% of all mRNAs during lactation, two are salivary-specific and one has dual specificity. We probed the function of eight candidate enhancers through experimental mouse genetics. Deletion of the super-enhancer led to a 98% reduced expression ofCsn3andFdcspin mammary and salivary glands, respectively, and Odam expression was abolished in both tissues. The other three casein genes were only marginally affected. Notably, super-enhancer activity requires the additional presence of a distalCsn3-specific enhancer. Our work identifies an evolutionary playground on which regulatory duality of a multigene locus was attained through an ancestral super-enhancer active in mammary and salivary tissue and gene-specific mammary enhancers.