bluuebunny/crossref_metadata_2025 huggingface dataset:
Compared With Conventional Insemination, Intracytoplasmic Sperm Injection Provides No Benefit in Cases of Nonmale Factor Infertility as Evidenced by Comparable Euploidy Rate
Authors: Patel Karishma , Vaughan Denis A. , Rodday Angie Mae , Penzias Alan , Sakkas Denny
Published: November 2023

(Abstracted from Fertil Steril 2023;120(2))

Intracytoplasmic sperm injection (ICSI) has dramatically improved fertilization rates for couples with male factor infertility and those with prior failed in vitro fertilization (IVF) cycles. Although several international academic organizations and the cumulative evidence do not suggest the routine use of ICSI for nonmale factor infertility, it is now used frequently for all cases of IVF regardless of the indication.
Association of Clinical Trial Participation With Improved Overall Survival for Recurrent, Platinum-Resistant Ovarian Cancer
Authors: Yao Molly Morton Meng , Chalif Julia , Lampert Erika J. , Chau Danielle , Rose Peter G. , Debernardo Robert , Michener Chad M. , Vargas Roberto , Chambers Laura M.
Published: November 2023

(Abstracted from Obstet Gynecol 2023;1(00):00)

Despite recent advancements in treatment, ovarian cancer remains the leading cause of gynecologic cancer death in the United States. Advanced ovarian cancer is treated using surgery and platinum-based chemotherapy but ultimately recurs in most patients and becomes resistant to platinum chemotherapy.
Comparison of Maternal Labor-Related Complications and Neonatal Outcomes Following Elective Induction of Labor at 39 Weeks of Gestation vs Expectant Management: A Systematic Review and Meta-analysis
Authors: Hong James , Atkinson Jessica , Mitchell Alexandra Roddy , Tong Stephen , Walker Susan P. , Middleton Anna , Lindquist Anthea , Hastie Roxanne
Published: November 2023

(Abstracted from JAMA Network Open 2023;6(5):e2313162)

Induction of labor historically has been discouraged when there is no medical indication, such as for postterm pregnancies, suspected cases of poor fetal growth, prelabor rupture of membranes, or hypertension. This is because elective induction is associated with a higher risk of cesarean delivery (CD) and adverse birth outcomes than spontaneous labor.
National Survey on the Emergency Department Management of Febrile Infants 29 to 60 Days Old With an Abnormal Urinalysis
Authors: Chapur Jeronimo , Meckler Garth , Doan Quynh , Bone Jeffrey N. , Burstein Brett , Sabhaney Vikram ,   on behalf of Pediatric Emergency Research Canada
Published: November 2023

Objectives

Recent clinical practice guidelines recommend that decisions regarding lumbar puncture (LP) for febrile infants older than 28 days should no longer be based on urinalysis results, but rather independently determined by inflammatory markers and sometimes guided by shared decision-making (SDM). This study sought to assess management decisions for febrile infants aged 29 to 60 days with an abnormal urinalysis.

Methods

A scenario-based survey was sent to emergency department physicians at all 15 Canadian tertiary pediatric centers. Participants were asked questions regarding management decisions when presented with a well-appearing febrile infant in the second month of life with either an abnormal or normal urinalysis.

Results

Response rate was 50.2% (n = 116/231). Overall, few respondents would perform an LP based on either an abnormal or normal urinalysis alone (10.3% and 6.0%, respectively). However, regression analysis demonstrated that decisions regarding LP were influenced by urinalysis results (P < 0.001), with respondents more likely to defer to inflammatory marker results for infants with a normal urinalysis result (57.8%) compared with those with an abnormal urinalysis (28.4%). Hospitalization (62.1%) and empiric antibiotic treatment by intravenous route (87.9%) were both frequent for low-risk infants with an abnormal urinalysis. Nearly half of respondents reported rarely (<25% of encounters) engaging families in SDM regarding LP decisions.

Conclusions

Knowledge translation initiatives reflecting current evidence should target use of inflammatory markers rather than urinalysis results to guide decisions regarding LP. Efforts emphasizing outpatient management with oral antibiotics and SDM for low-risk infants with an abnormal urinalysis could also further align management with current evidence and guidelines.
Predictors for Dental Intervention in Children After Dental Injury: A Retrospective Analysis and Literature Review
Authors: Cohen Neta , Via -Kagan Renana , Haberman Shira , Gigi Dana , Ianculovici Clariel , Rimon Ayelet
Published: November 2023

Objective

This study aimed to explore risk factors for dental intervention in patients presenting to the pediatric emergency department (PED) after dental injury.

Methods

We retrospectively explored patients aged 0 to 18 years who presented to our PED between 2017 and 2021 after dental injury.

Results

Of the total of 830 patients (mean age 7.1 ± 3.9 years, 589 [71.0%] male patients), 237 (28.5%) required dental intervention. All patients with alveolar fractures and those with involvement of permanent teeth with extrusive luxation mandated urgent dental consultation. Additional independent predictors for dental intervention for primary tooth injury were: root fracture (adjusted odds ratio [aOR] 38.4; 95% confidence interval [CI], 3.95–373.22; P = 0.002), facial bone involvement (aOR 12.40; 95% CI, 2.33–65.93; P = 0.003), lateral luxation (aOR 6.9; 95% CI, 4.27–11.27; P < 0.001), extrusive luxation (aOR 6.44; 95% CI, 2.74–15.14; P < 0.001), and avulsion (aOR 2.06; 95% CI, 1.23–3.45; P = 0.006). Additional independent predictors for permanent tooth injury were lateral luxation (aOR 27.8; 95% CI, 6.1–126.6; P < 0.001) and avulsion (aOR 6.8; 95% CI, 2.9–15.9; P < 0.001).

Conclusions

Alveolar fracture is a severe dental injury, requiring intervention, for primary and permanent teeth injuries. Tooth luxation with significant mobility or malocclusion, incomplete avulsion, a suspected root involvement, or facial bone injury in the primary teeth and tooth luxation (extrusive/lateral) and avulsion in the permanent teeth dictate urgent dental consultation and intervention. Clinical algorithms for dental injury management are suggested.
Clonal hematopoiesis of indeterminate potential in persons with HIV
Authors: Knudsen Andreas D. , Eskelund Christian Winther , Benfield Thomas , Zhao Yanan , Gelpi Marco , Køber Lars , Trøseid Marius , Kofoed Klaus F. , Ostrowski Sisse R. , Reilly Cavan , Borges Álvaro H. , Grønbæk Kirsten , Nielsen Susanne D.
Published: November 2023

Background:

Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH).

Methods:

From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis.

Results:

In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A, TET2, and ASXL1, accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1β, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses.

Conclusion:

In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.
Geographic variations of pre-exposure prophylaxis reversal and abandonment among United States counties
Authors: Dawit Rahel , Goedel William C. , Reid Sean C. , Doshi Jalpa A. , Nunn Amy S. , Chan Philip A. , Dean Lorraine T.
Published: November 2023

Objective:

In the United States, one in five newly insurer-approved pre-exposure prophylaxis (PrEP) prescriptions are reversed with over 70% of those reversed, being abandoned. Given the Ending the HIV Epidemic (EHE) initiative's goals, we assessed geographic variations of PrEP reversal and abandonment across EHE and non-EHE counties in the United States.

Design:

This was a cross-sectional analysis of secondary data.

Methods:

Data were collected from Symphony Analytics for adults 18 years and older, with a newly prescribed PrEP claim. Using the proportion of PrEP prescriptions by county, hotspot analysis was conducted utilizing Getis Ord Gi∗ statistics stratified by EHE and non EHE counties. Multivariable logistic regression was used to identify factors associated with residing in hotspots of PrEP reversal or PrEP abandonments.

Results:

Across 516 counties representing 36,204 patients, the overall PrEP reversal rate was 19.4%, whereas the PrEP abandonment rate was 13.7%. Reversals and abandonments were higher for non-EHE (22.7 and 17.1%) than EHE (15.6 and 10.5%) counties. In both EHE and non-EHE counties, younger age, less education, females, and an out-of-pocket cost of greater than $100, were significantly associated with greater likelihood of residing in hotspots of PrEP reversal or abandonment, while Hispanics, Medicaid recipients, and an out-of-pocket cost of $10 or less had lower likelihood of residing in hotspots of reversal and abandonment.

Conclusion:

Findings indicate the need for implementation of focused interventions to address disparities observed in PrEP reversal and abandonment. Moreover, to improve primary PrEP adherence, national PrEP access programs should streamline and improve PrEP accessibility across different geographic jurisdictions.
Subnodal Correspondence of PSMA Expression and USPIO-MRI in Metastatic Pelvic Lymph Nodes in Prostate Cancer
Authors: Schilham Melline Gabrielle Maria , Somford Diederik M. , Veltien Andor , Zamecnik Patrik , Barentsz Jelle O. , Sedelaar Michiel J.P.M. , Kusters-Vandevelde Heidi V.N. , Gotthardt Martin , Rijpkema Mark , Scheenen Tom W.J.
Published: November 2023

Objectives

Two advanced imaging modalities used to detect lymph node (LN) metastases in prostate cancer patients are prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography and ultrasmall superparamagnetic iron oxide (USPIO)–enhanced magnetic resonance imaging (MRI). As these modalities use different targets, a subnodal comparison is needed to interpret both their correspondence and their differences. The aim of this explorative study was to compare ex vivo 111In-PSMA μSPECT images with high-resolution 7 T USPIO μMR images and histopathology of resected LN specimens from prostate cancer patients to assess the degree of correspondence at subnodal level.

Materials and Methods

Twenty primary prostate cancer patients who underwent pelvic LN dissection were included and received USPIO contrast and 111In-PSMA. A total of 41 LNs of interest (LNOIs) were selected for ex vivo imaging based on γ-probe detection or palpation. μSPECT and μMRI acquisition were performed immediately after resection. Overlay of μSPECT images on MR images was performed, and the level of correspondence (LoC) between μSPECT and μMR findings was assessed according to a 4-point Likert classification scheme.

Results

Forty-one LNOIs could be matched to an LN on ex vivo μMRI. Coregistration of μSPECT and USPIO-enhanced water-selective multigradient echo MR images was successful for all 41 LNOIs. Ninety percent of the lesions showed excellent correspondence regarding the presence of metastatic tissue and affected subnodal site (LoC 4; 37/41). In only 1 of 41 LNOIs, a small metastasis was misclassified by both techniques. Three LNOIs were classified as LoC 3 (7%) and 1 LNOI as LoC 2. All LoC 2 and LoC 3 lesions had PSMA-expressing metastases on final histopathology

Conclusions

Coregistration of μSPECT and USPIO-μMRI showed excellent subnodal correspondence in the majority (90%) of LNs. Ex vivo imaging may thus help localize small cancer deposits within resected LNs and could contribute to improved interpretation of in vivo imaging of LNs.
68Ga-PSMA-11 PET/CT and 64CuCl2 PET/CT Help in Identifying Rare Metastatic Site of Penile Shaft in a Patient of Carcinoma Prostate
Authors: Verma Priyanka , Nazar Aamir , Jadhav Sonali , Basu Sandip
Published: November 2023

A 71-year-old man, presenting with complaints of burning sensation and pain during urination, finally diagnosed with prostate carcinoma. Ultrasonography of the abdomen and pelvis revealed prostatomegaly. Serum PSA level was elevated, and TRUS-guided biopsy demonstrated acinar adenocarcinoma (Gleason score: 5 + 4 = 9).68Ga-PSMA-11 PET/CT for initial staging showed PSMA-avid enlarged prostate, pelvic lymphadenopathy, and focal PSMA uptake in the left side of the shaft of the penis. The patient also underwent a64CuCl2PET/CT, which demonstrated similar findings of enlarged prostate and adenopathy with focally increased tracer uptake in the shaft of the penis coinciding with the lesion observed on68Ga-PSMA-11 PET/CT, thereby detecting a rare metastatic site from carcinoma prostate.
“Hepatic Superscan” Revealed on 18F-FDG PET Due to Drug-Induced Fulminant Hepatitis
Authors: Qiu Guigang , Shao Fuqiang , Xie Peng
Published: November 2023

“Hepatic superscan” could be caused by a variety of etiologies. Here we report a 68-year-old woman with a medication history of cefoperazone and azithromycin for pneumonia recently who underwent 18F-FDG PET/CT to detect underlying malignancy due to unexplained liver damage and fever of unknown origin. Unexpectedly, “hepatic superscan” without morphologic changes was noted. Unfortunately, aggressive treatment did not reverse the damaged liver function, and the patient rapidly died. Drug-induced fulminant hepatitis was diagnosed clinically. Our case demonstrates that fulminant hepatitis could result in “hepatic superscan” on 18F-FDG PET despite negative findings on the ultrasonography, CT, and MRI.
FDG PET/CT in Pancreatic Ductal Adenocarcinoma Arising From a Heterotopic Pancreas of the Pylorus
Authors: Ji Xia , Dong Aisheng , Wang Yang
Published: November 2023

Malignant transformation of heterotopic pancreas is extremely rare. We describe FDG PET/CT findings in a case of pancreatic ductal adenocarcinoma arising from a heterotopic pancreas in the submucosa of the pylorus with peripyloric lymph node metastasis and elevated serum carbohydrate antigen 19-9 level. The heterotopic pancreatic adenocarcinoma showed intense FDG uptake, and the peripyloric lymph node metastasis showed mild FDG uptake. This case indicates that heterotopic pancreatic adenocarcinoma should be included in the differential diagnosis of FDG-avid gastric submucosal lesions, especially in patients with elevated serum carbohydrate antigen 19-9 level.
FAPI Uptake in Gallbladder Is It Normal Biodistribution?
Authors: Behnam-Manesh Hossein , Doroudinia Abtin , Bayat Mohadeseh , Bakhshayesh Karam Mehrdad , Salimi Babak , Nejabat Marzieh , Mehrian Payam
Published: November 2023

Radiolabeled fibroblast activation protein inhibitors (FAPIs) have been extensively used in different types of cancers, although not yet FDA approved. Normal patterns of FAPI biodistribution have been investigated, and it is known that FAPI is expressed in nonmalignant pathophysiological lesions, characterized by tissue remodeling such as atherosclerosis, arthritis, and scar/fibrotic tissues. In this interesting image, we are presenting the accumulation of 68Ga-FAPI in the gallbladder. This finding could be related to a normal distribution of the radiotracer as a physiologic finding. This is a potentially important finding as FAPI may be used as theragnostic agent in the future.
Deep Learning-based Assessment of Facial Asymmetry Using U-Net Deep Convolutional Neural Network Algorithm
Authors: Jeon Sang-Min , Kim Seojeong , Lee Kyungmin Clara
Published: November 2023

Objectives:

This study aimed to evaluate the diagnostic performance of a deep convolutional neural network (DCNN)-based computer-assisted diagnosis (CAD) system to detect facial asymmetry on posteroanterior (PA) cephalograms and compare the results of the DCNN with those made by the orthodontist.

Materials and Methods:

PA cephalograms of 1020 patients with orthodontics were used to train the DCNN-based CAD systems for autoassessment of facial asymmetry, the degree of menton deviation, and the coordinates of its regarding landmarks. Twenty-five PA cephalograms were used to test the performance of the DCNN in analyzing facial asymmetry. The diagnostic performance of the DCNN-based CAD system was assessed using independent t-tests and Bland-Altman plots.

Results:

Comparison between the DCNN-based CAD system and conventional analysis confirmed no significant differences. Bland-Altman plots showed good agreement for all the measurements.

Conclusions:

The DCNN-based CAD system might offer a clinically acceptable diagnostic evaluation of facial asymmetry on PA cephalograms.
Clinical impact of molecular profiling in rare brain tumors
Authors: Pratt Drew , Penas-Prado Marta , Gilbert Mark R.
Published: November 2023

Purpose of review

The purpose of this review is to describe the commonly used molecular diagnostics and illustrate the prognostic importance to the more accurate diagnosis that also may uncover therapeutic targets.

Recent findings

The most recent WHO Classification of Central Nervous System Tumours (2021) lists over 100 distinct tumor types. While traditional histology continues to be an important component, molecular testing is increasingly being incorporated as requisite diagnostic criteria. Specific molecular findings such as co-deletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q) now define IDH-mutant gliomas as oligodendroglioma. In recent years, DNA methylation profiling has emerged as a dynamic tool with high diagnostic accuracy. The integration of specific genetic (mutations, fusions) and epigenetic (CpG methylation) alterations has led to diagnostic refinement and the discovery of rare brain tumor types with distinct clinical outcomes. Molecular profiling is anticipated to play an increasing role in routine surgical neuropathology, although costs, access, and logistical concerns remain challenging.

This review summarizes the current state of molecular testing in neuro-oncology highlighting commonly used and developing technologies, while also providing examples of new tumor types/subtypes that have emerged as a result of improved diagnostic precision.
Non typhoidal Salmonella causing urinary tract infection in a young male with renal calculi- a case report and comprehensive review
Authors: Sriramajayam Lavanya , Boopathy Vijayaraghavan Krishna Mohan , Appalaraju Boppe , Jeyaraj Sankarganesh
Published: November 2023

Non typhoidal Salmonella (NTS) causes urinary tract infections infrequently and are usually associated with presence of genitourinary abnormalities.
Case Presentation:
We report a case of immunocompetent male in his early 20s with phimosis presented with history of dysuria and burning micturition for 4 months. A renal ultrasonography showed presence of bilateral intrarenal calculi. Urine analysis revealed presence of non typhoidal Salmonella. Automated identification systems performed poorly in identification of serotype. On serotyping, it was identified as Salmonella enteritidis in the referral centre. The patient was managed with oral antibiotics.
Conclusion:
This report highlights the issues of inaccurate identification of NTS even with advanced automated systems and early initiation of therapy based on the knowledge of local susceptibility patterns. UTI in immunocompetent individuals by non typhoidal salmonellae should always be investigated further to rule out genitourinary abnormalities and appropriate antibiotics must be started to avoid chronicity and complications.
Clinical and Microbiological Characteristics of Rare Pathogens Causing Bacteremia in Patients Admitted to a Tertiary Care Centre in Northern India
Authors: Tejan Nidhi , Kar Mitra , Singh Romya , Jamwal Ashima , Dubey Akanksha , Choudhary Radhika , Sahu Chinmoy , Patel Sangram Singh , Kumari Pooja , Ghar Malay
Published: November 2023

Introduction: The use of newer diagnostic and therapeutic procedures, broad-spectrum antibiotics, and, chemotherapy increases susceptibility to bacteremia. Rise of new bacterial pathogens raises innumerable concerns like virulence capacity, and susceptibility profiles of these organisms.
Hypothesis/Gap Statement: Information about the incidence and risk factors of bacteremia caused by rare pathogens from India is limited.
Aim: We conducted this study to identify the risk factors and underlying conditions predisposing to bacteremia by rare pathogens and analyze the antibiotic resistance pattern of the isolates.
Methodology: This retrospective study was performed on 64 rare isolates collected from blood culture from January 2022 to December 2022. All clinical and laboratory data was obtained from laboratory registers and the electronic information system and later analyzed by using SPSS statistical software (IBM SPSS version 20, Armonk, N.Y.).
Result: Sixty-four rare pathogenic gram-negative bacteria (GNB) were identified from blood culture. Mean age of patients was 36.60 ± 21.83 years, with 56.25% (36/64, 56.25%) men. Malignancies (25/64, 39.06%) were the most common comorbidity in the patients. Burkholderia cenocepacia (21/64, 32.81%) was the most common microorganism followed by Ochrobactrum spp (16/64, 25.0%). During hospitalization, 17.19% (11/64, 17.19%) patients had indwelling catheterization, 40.63% (26/6, 40.63%) patients underwent surgical procedures and 32.81% (21/64, 32.81%) patients had chemo port in-situ. Out of 64 patients, 13 (13/64, 20.31%) patients died due to the direct effect of bacteremia caused by these isolates.
Conclusion: This study represents the rare pathogens identified from bloodstream infections and evaluates their susceptibility pattern to aid the clinicians’ knowledge.
The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics
Authors: Yap Justin , Kayda Iryna , Asamoah-Boaheng Michael , Haig Scott , Kirkham Tracy , Cheskes Sheldon , Demers Paul , Goldfarb David , Grunau Brian
Published: November 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273}). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42%) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61% (IQR 39.44-92.82) and 98.60% (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Wuhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.
TRANSITION FROM CLINICAL PRACTITIONER TO ACADEMIC EDUCATOR: THE EXPERIENCES OF RADIOGRAPHY LECTURERS IN NIGERIA
Authors: Ogolodom Michael Promise , Chiegwu H.U. , Mbaba Awajimijan Nathaniel , Bakre Abdul Fatai K. , Balogun Elizabeth O. , Obasi Annmaris Chimebere , Ezechukwu Uchenna Norochukwunso , Ezugwu Emeka E. , Egop Egop Brownson
Published: November 2023

BackgroundClinical educators are essential in radiography education programmes. Transitioning from clinical practicing radiographers to academic educators is a rewarding journey. This study was designed to examine the experience of Radiography Lecturers in the Nigerian universities that converted from radiography practitioners to academic educators.Materials and methods:A Google form questionnaire-based study design was conducted among 35 radiography lecturers in Nigeria. Only lecturers in Nigerian Universities who had worked as radiography clinical practitioners before transited to academics and consented to participate in this study were included. The questionnaire captured responses on socio-demographic variables, challenges, barriers, successes of transition from practitioners to academic educators.Results:The majority 17(48.6%) of the respondents earned income of above #251,000.00 as a practicing radiographers. Of the 35 respondents, the majority 12(34.3%) each respectively earned #101,000.00 −#150,000.00 and #151,000.00 - #200,000.00 as an academic radiographers. Majority 17(48.6%) of the respondents agreed that the main challenge they are encountering as an academic educator is rigorous research activities. Family issues affected smooth transition process as 23(65.7%) of the respondents agreed to that. Majority 18(51.4%) perceived mentorship as the key factor responsible for smooth transition from practice to academic. There was statistically significant relationship between gender and challenges encountered by the responders (χ2= 28.194, p = 0.00).Conclusion:The respondents experienced different challenges as they transited from clinical practice to academic. Mentorship is the key factor that militated against the smooth transition process. There was statistically significant relationship between gender and challenges encountered by the responders.
Statistical Analysis Plan for Dynamic HIV Choice Prevention delivered with Community Health Workers in Phase A of SEARCH-Sapphire
Authors: Balzer Laura B. , Kakande Elijah R. , Ayieko James , Kabami Jane , Chamie Gabriel , Kamya Moses R. , Havlir Diane V. , Petersen Maya L. ,   SEARCH Collaboration
Published: November 2023

This document provides the statistical analytic plan (SAP) for a cluster randomized trial evaluating the effect of community-based Dynamic Choice HIV Prevention (DCP) intervention, delivered by community health workers in rural Uganda and Kenya (Clinicaltrials.gov:NCT04810650). The SAP was locked prior to unblinding and effect estimation.
Prevalence and risk factors of low back pain among nursing students
Authors: Liya Jin , Ya Zhu , Miaoye Hu , Chunmei Zhang
Published: November 2023

Study design

Retrospective case-control study

Objective

To investigate the incidence of low back pain among nursing students and to analyze the factors contributing to low back pain among nursing students.

Method

This retrospective study was conducted in 78 nursing students who entered our hospital for internship from July 2022 to March 2023. Demographic data, including age, gender, height, weight, exercise habits, staying-up-late habits, smoking history, education level, mental status, working posture, menstrual pain, and other basic information were collected, and the number of interns experiencing low back pain in the past 1 month and 3 months was recorded to investigate the incidence of low back pain among nursing students. Relevant risk factors were also analyzed.

Results

The incidence of low back pain among nursing students was 19.2% within 1 month and 25.6% within 3 months. Factors such as gender, age, height, weight, smoking history, exercise habits, staying-up-late habits, education level, mental status, working posture correctness, and menstrual pain showed no statistical significance between the pain and non-pain groups (P> 0.05), while BMI and exercise habits showed statistical differences between the two groups (P< 0.05). BMI (OR= 1.530; 95% confidence interval = 1.16 - 2.02;P= 0.003) was identified as a risk factor for low back pain. Exercise habits (OR= 0.232; 95% confidence interval = 0.07 - 0.81;P= 0.022) were identified as protective factors for low back pain.

Conclusion

The incidence of low back pain among nursing students remains relatively high, and low back pain is associated with high BMI and lack of exercise. These results can provide a reference for developing preventive measures for low back pain among nursing students.
Bacterial assembly in the switchgrass rhizosphere is shaped by phylogeny, host genotype, and growing site
Authors: Sutherland Jeremy , Bell Terrence H. , Bonos Stacy , Tkach Christopher , Hansen Julie , Crawford Ryan , Carlson John E. , Lasky Jesse R.
Published: November 2023

Since microbial traits are conserved at different taxonomic levels, plant hosts may influence microbiome composition differently at different levels to broadly promote or resist microbiota with traits that impact host fitness. We tested this hypothesis by assessing signals of host genetic influence on bacterial composition in the switchgrass rhizosphere using 128 genotypes in dissimilar growing sites.

We employed three common gardens, combined with host genetic mapping, 16S rRNA gene sequence analysis, hierarchical modeling, tests of phylogenetic conservation of host influence, and genome-wide association analyses to determine the contributions of host genetics in shaping rhizosphere bacterial composition at different taxonomic levels.

Modeling bacterial assembly showed that growing site was a strong factor shaping bacterial composition in the rhizosphere, though host genetic influence played a significant role. The heritability of bacterial abundance was strongest at the genus level. Phylogenetic signal for heritability was detected within the bacterial phylogeny but conserved clades differed between common gardens. We identified shared host genetic variants associated with bacterial abundance and host traits related to plant metabolism.

Our results suggest further investigation is required regarding the genotype-by-environment-by-microbiome relationship to elucidate the factors shaping rhizosphere microbiome composition and the agroecological dynamics shaping plant phenotype.
Active learning for medium optimization for selective bacterial culture
Authors: Zhang Shuyang , Aida Honoka , Ying Bei-Wen
Published: November 2023

Medium optimization and development for selective bacterial culture are essential for isolating and functionalizing individual bacteria in microbial communities; nevertheless, it remains challenging due to the unknown mechanisms between bacterial growth and medium components. The present study first tried combining machine learning (ML) with active learning to finetune the medium components for the selective culture of two divergent bacteria, i.e.,Lactobacillus plantarumandEscherichia coli. ML models considering multiple growth parameters of the two bacterial strains were constructed to predict the finetuned medium combinations for higher specificity of bacterial growth. The growth parameters were designed as the exponential growth rate (r) and maximal growth yield (K), which were calculated according to the growth curves. The eleven chemical components in the commercially available medium MRS were subjected to medium optimization and specialization. High-throughput growth assays of both strains grown separately were performed to obtain thousands of growth curves in more than one hundred medium combinations, and the resultant datasets linking the growth parameters to the medium combinations were used for the ML training. Repeated rounds of active learning (i.e., ML model construction, medium prediction, and experimental verification) successfully improved the specific growth of a single strain out of the two. BothrandKshowed maximized differentiation between the two strains. Further analysis of all data accumulated in active learning identified the decision-making medium components for growth specificity and the differentiated determinative manner of growth decision of the two strains. In summary, this study demonstrated the efficiency and practicality of active learning in medium optimization for selective culture and offered novel insights into the contribution of the chemical components to specific bacterial growth.
Computationally Driven Design of Novel BACE-1 Inhibitors for Alzheimer’s Disease
Authors: Chinn Megan M. , Mateos Diego Lopez , Riley Mary A. , Siegel Justin B.
Published: November 2023

Alzheimer’s disease is the most common form of dementia affecting 35 million people globally. One of the major efforts in the development of a treatment for Alzheimer’s is to reduce the rate of plaque formation, the common hallmark of Alzheimer’s disease. The protease BACE-1 has been demonstrated to play a role in catalyzing plaque formation and is therefore a major drug target. Here we report potential new drug candidates building upon Verubecestat, developed through computationally driven molecular modeling methods. Both designed molecules have improved docking scores relative to Verubecestat when modeled in the BACE-1 active site, and therefore present potential new leads for more effective therapeutics to combat Alzheimer’s disease.
SAP expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis
Authors: Gartshteyn Yevgeniya , Geraldino-Pardilla Laura , Khalili Leila , Bukhari Shoiab , Lerrer Shalom , Askanase Anca D. , Mor Adam
Published: November 2023

Introduction

T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co -stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell – B cell interactions. SAP and SLAMF are critical for TPH dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. Additionally, we analyzed SAP expression from renal infiltrating lupus nephritis (LN) T cells using the publicly available single-cell RNA sequencing (sc-RNA seq) Accelerated Medicines Partnership (AMP) in SLE dataset.

Results

PBMCs from 30 patients with SLE (34±10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5±2.6 vs. 41.3±3.4, p=0.007 and 52.5±3.0 vs. 39.2±2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity, SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells identified increased SAP from LN compared with control kidney biopsy samples (p=0.03), including an expansion of SAP-positive TFH-like subsets in the LN kidneys. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 as well as granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells and granzyme K positive effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs.

Conclusion

The expansion of SAP expressing T helper cells was associated with lupus nephritis in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved understanding of SLAM/SAP signaling can identify new therapeutic targets in LN.
Exclusion of PD-1 from the immune synapse: a novel strategy to modulate T cell function
Authors: Hao Luke Yi , Lerrer Shalom , Song Ruijiang , Goeckeritz Michael , Hu Xizi , Mor Adam
Published: November 2023

Targeting immune checkpoint receptors on T cells is a common cancer treatment strategy. Frequently, this is accomplished through antibodies targeting the ligand of inhibitory co-receptors. Blocking the immune checkpoint PD-1 binding to its ligands PD-L1 and PD-L2 prevents downstream signaling and enhances anti-tumor T cell responses. This approach improved cancer patients’ outcome. However, only one-third of the patients respond to these treatments. To better understand the mechanism of anti-PD-1 antibodies, we explored the location of PD-1 within the immune synapse. Surprisingly, we discovered that anti-PD-1 antibodies, besides blocking the interaction between PD-1 and its ligands, also removed PD-1 from the synapse. We demonstrated a correlation between removing PD-1 from the synapse by anti-PD-1 antibodies and the extent of T cell activation. Interestingly, a short version of the anti-PD-1 antibody, F(ab’)2, failed to remove PD-1 from the synapse and activate T cells. Using syngeneic tumor model, we showed a superior anti-tumor effect to anti-PD-1 antibody over the shorter version of the antibody. Our data indicates that anti-PD-1 antibodies activate T cells by removing PD-1 away from the synapse and changing the location of PD-1 or other immune receptors within immune synapse could serve as an alternative, efficient approach to treat cancer.
An automated archival single-nucleus total RNA sequencing platform mapping integrative and retrospective cell atlas of gliomas
Authors: Xu Ziye , Chen Lingchao , Lin Xin , Lyu Yuexiao , Zhou Mofei , Chen Haide , Zhang Heng , Zhang Tianyu , Chen Yu , Suo Yuanzhen , Liang Qian , Qin Zhiyong , Wang Yongcheng
Published: November 2023

Single-cell RNA sequencing (scRNA-seq) has dramatically transformed biomedical research within laboratory settings. It has been extensively employed to investigate the heterogeneity and plasticity of glioma, the most prevalent brain tumor. However, the clinical diagnosis and treatment of glioma remain complex and challenging, highlighting the need for comprehensive cancer research. Currently available scRNA-seq platforms are insufficient to fulfill the demands posed by large-scale clinical applications. Here, we present an automated high-throughput single-nucleus total RNA sequencing platform, known as AAsnRandom-seq. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, designed to accommodate a diverse range of sample types. The performance and versatility of AAsnRandom-seq are validated using over one hundred clinical FFPE and frozen samples. AAsnRandom-seq was applied to archival FFPE samples of various glioma subtypes, including rare clinical samples, and matched primary-recurrent glioblastomas (GBMs), delving into the comprehensive molecular characteristic of glioma at single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles within different glioma clusters are detected. Promising recurrence-related targets and pathways are identified from the matched primary-recurrent GBMs. AAsnRandom-seq holds significant application value on large-scale integrative and retrospective clinical research using archived specimens.
rNMPID: a database for riboNucleoside Mono-Phosphates In DNA
Authors: Yang Jingcheng , Sun Mo , Ran Zihan , Yang Taewhan , Kundnani Deepali L. , Storici Francesca , Xu Penghao
Published: November 2023

Motivation

Ribonucleoside monophosphates (rNMPs) are the most abundant non-standard nucleotides embedded in genomic DNA. If the presence of rNMP in DNA cannot be controlled, it can lead to genome instability. The actual positive functions of rNMPs in DNA remain mainly unknown. Considering the association between rNMPs embedment and various diseases and cancer, the phenomenon of rNMPs embedment in DNA has become a prominent area of research in recent years.

Results

We introduce the rNMPID database, which is the first database revealing rNMP-embedment characteristics, strand bias, and preferred incorporation patterns in the genomic DNA of samples from bacterial to human cells of different genetic backgrounds. The rNMPID database uses datasets generated by different rNMP-mapping techniques. It provides the researchers with a solid foundation to explore the features of rNMPs embedded in the genomic DNA of multiple sources, and their association with cellular functions, and, in future, disease. It also significantly benefits researchers in the fields of genetics and genomics who aim to integrate their studies with the rNMP-embedment data.

Availability

rNMPID is freely accessible on the web athttps://www.rnmpid.org.

Contact

xph6113@gmail.comorstorici@gatech.edu
The bidirectional effects between cognitive ability and brain morphology: A life course Mendelian randomization analysis
Authors: Korologou-Linden Roxanna , Schuurmans Isabel K. , Cecil Charlotte A.M. , White Tonya , Banaschewski Tobias , Bokde Arun L.W. , Desrivières Sylvane , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Holz Nathalie , Fröhner Juliane H. , Smolka M , Walter Henrik , Winterer Jeanne , Whelan Robert , Schumann Gunter , Howe Laura D , Ben-Shlomo Yoav , Davies Neil M , Anderson Emma L
Published: November 2023

Introduction

Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area.

Methods

Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years).

Results

The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability.

Discussion

Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.
A multi-task domain-adapted model to predict chemotherapy response from mutations in recurrently altered cancer genes
Authors: Jayagopal Aishwarya , Walsh Robert J. , Hariprasannan Krishna Kumar , Mariappan Ragunathan , Mahapatra Debabrata , Jaynes Patrick William , Lim Diana , Tan David Shao Peng , Tan Tuan Zea , Pitt Jason J. , Jeyasekharan Anand D. , Rajan Vaibhav
Published: November 2023

Next generation sequencing (NGS) of tumours is increasingly utilised in oncological practice, however only a minority of patients harbour oncogenic driver mutations benefiting from targeted therapy. Development of a drug response prediction (DRP) model based on available genomic data is important for the ‘untargetable’ majority of cases. Prior DRP models typically rely on whole transcriptome and whole exome sequencing (WES), which is often unavailable in clinical practice. We therefore aim to develop a DRP model towards repurposing of standard chemotherapy, requiring only information available in clinical grade NGS (cNGS) panels of recurrently mutated genes in cancer. Such an approach is challenging due to the sparsity of data in a restricted gene set and limited availability of patient samples with documented drug response. We first show that an existing DRP performs equally well with whole exome data and a cNGS subset comprising ∼300 genes. We then develop Drug IDentifier (DruID), a DRP model specific for restricted gene sets, using a novel transfer learning-based approach combining variant annotations, domain-invariant representation learning and multi-task learning. Evaluation of DruID on pan-cancer data (TCGA) showed significant improvements over state-of-the-art response prediction methods. Validation on two real world - colorectal and ovarian cancer - clinical datasets showed robust response classification performance, suggesting DruID to be a significant step towards a clinically applicable DRP tool.
Riboswitch and small RNA modulatebtuBtranslation initiation inEscherichia coliand trigger distinct mRNA regulatory mechanisms
Authors: Bastet L. , Korepanov A.P. , Jagodnik J. , Grondin J.P. , Lamontagne A.M. , Guillier M. , Lafontaine D.A.
Published: November 2023

Small RNAs (sRNAs) and riboswitches represent distinct classes of RNA regulators that control gene expression upon sensing metabolic or environmental variations. While sRNAs and riboswitches regulate gene expression by affecting mRNA and protein levels, existing studies have been limited to the characterization of each regulatory system in isolation, suggesting that sRNAs and riboswitches target distinct mRNA populations. We report that the expression ofbtuBinEscherichia coli, which is regulated by an adenosylcobalamin (AdoCbl) riboswitch, is also controlled by the small RNAs OmrA and, to a lesser extent, OmrB. Strikingly, we find that the riboswitch and sRNAs reduce mRNA levels through distinct pathways. Our data show that while the riboswitch triggers Rho-dependent transcription termination, sRNAs rely on the degradosome to modulate mRNA levels. Importantly, OmrA pairs with thebtuBmRNA through its central region, which is not conserved in OmrB, indicating that these two sRNAs may have specific targets in addition to their common regulon. In contrast to canonical sRNA regulation, we find that OmrA repression ofbtuBis lost using an mRNA binding-deficient Hfq variant. Together, our study demonstrates that riboswitch and sRNAs modulatebtuBexpression, providing an example ofcis-andtrans-acting RNA-based regulatory systems maintaining cellular homeostasis.