bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study
Authors: Zhao Xiaofeng , Zhang Rong , Song Shufang , Wang Yu , Mu Xiaojie
Published: June 2024

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.
The physiological basis of renal nuclear medicine
Authors: Peters Adrien Michael
Published: June 2024

Renal physiology underpins renal nuclear medicine, both academic and clinical. Clearance, an important concept in renal physiology, comprises tissue uptake rate of tracer (tissue clearance), disappearance rate from plasma (plasma clearance), appearance rate in urine (urinary clearance) and disappearance rate from tissue. In clinical research, steady-state plasma clearances of para-amino-hippurate and inulin have been widely used to measure renal blood flow (RBF) and glomerular filtration rate (GFR), respectively. Routinely, GFR is measured at non-steady state as plasma clearance of a filtration agent, such as technetium-99m diethylenetriaminepentaacetic acid. Scaled to three-dimensional whole body metrics rather than body surface area, GFR in women is higher than in men but declines faster with age. Age-related decline is predominantly from nephron loss. Tubular function determines parenchymal transit time, which is important in renography, and the route of uptake of technetium-99m dimercaptosuccinic acid, which is via filtration. Resistance to flow is defined according to the pressure-flow relationship but in renography, only transit time can be measured, which, being equal to urine flow divided by collecting system volume, introduces further uncertainty because the volume is also unmeasurable. Tubuloglomerular feedback governs RBF and GFR, is regulated by the macula densa, mediated by adenosine and renin, and can be manipulated with proximal tubular sodium–glucose cotransporter-2 inhibitors. Other determinants of renal haemodynamics include prostaglandins, nitric oxide and dopamine, while protein meal and amino acid infusion are used to measure renal functional reserve. In conclusion, for measuring renal responses to exogenous agents, steady-state para-amino-hippurate and inulin clearances should be replaced with rubidium-82 and gallium-68 EDTA for measuring RBF and GFR.
The presentation of two rare idiopathic diseases in one patient: spontaneous idiopathic pneumoperitoneum and idiopathic gastroparesis: a case report
Authors: González-Acosta Isabela , Maldonado-García Edwin L. , López-Jasso Federico
Published: June 2024

Introduction:

Idiopathic gastroparesis (GP) is a syndrome characterized by delayed gastric emptying in the absence of a mechanical obstruction and the presence of cardinal symptoms, spontaneous idiopathic pneumoperitoneum is the presence of free air in the abdomen with the exclusion of a perforated viscera on endoscopy; both diseases have a low prevalence in which no detectable primary etiology can be identified. The authors present the case of a 44-year-old female with both diseases occurring simultaneously.

Presentation of case:

A 44-year-old female without relevant prior medical history, presented to the emergency room with intense abdominal pain in all four quadrants, on superficial and deep palpation. Imaging studies were conducted revealing the presence of a distended stomach filled with contrast and free air in the abdomen. An endoscopy was conducted looking for an obstruction of the gastric content and a laparotomy for the presence of a perforation on the viscera; both were ruled out.

Clinical discussion:

Although surgical intervention is not necessary on a patient presenting either with GP or spontaneous idiopathic pneumoperitoneum, given the clinical presentation and image studies of this patient with the finding of free air in the abdomen, a distended stomach filled with contrast and severe abdominal pain, it was decided to perform a laparotomy looking for a possible source and avoid complications of a possible blockage and/or perforation in the gastrointestinal tract.

Conclusion:

First-time cases pose a challenge for physicians at the moment of deciding on the best treatment option for the patient, especially with low-frequency pathologies.
Unanticipated discovery: incidental encounter with fasciola hepatica during ERCP – a case report
Authors: Sharma Pasanda , Sapkota Prakash , Gurung Ram Bahadur , Shrestha Nikesh Mani , Shrestha Sajan , Humagain Sankalpa , Tamang Ashish
Published: June 2024

Introduction and Importance:

Fasciola hepatica (FH) is a rare parasitic infection in humans. Its incidental detection during endoscopic retrograde cholangiopancreatography (ERCP) is exceptionally uncommon. This case underscores the importance of considering parasitic infections, even in low-endemicity regions, and the potential implications of dietary and environmental factors in disease transmission.

Case Presentation:

The authors present a case of a 31-year-old female from Dhading, Nepal, who underwent ERCP for suspected biliary stone. The patient had been experiencing recurring, nonradiating, burning epigastric pain for 5 to 7 years, which had recently intensified. Previous evaluations, including abdominal ultrasonography, CT, and MRI, revealed a dilation within the common bile duct and an obstruction in the biliary system.

Clinical Discussion:

During ERCP, cholangiography revealed mildly dilated extra and intrahepatic bile ducts with irregular filling defects in the common hepatic duct. Sphincterotomy was performed, followed by the extraction of multiple FH worms. A 7 Fr 7 cm double pigtail plastic stent was placed with a good flow of bile. However, the patient experienced anaphylaxis during the procedure, necessitating swift and tailored administration of appropriate medications to ensure effective management and stabilization. The patient was closely monitored in the ICU postprocedure.

Conclusion:

After careful monitoring and treatment, the patient fully recovered. The unexpected discovery of FH during ERCP is extremely rare. Early recognition and appropriate management of such incidental findings are crucial to ensuring optimal patient outcomes.
Unusual extrahepatic metastatic site of hepatocellular carcinoma with post-therapy disseminating metastases presenting as a primary soft tissue sarcoma: case report
Authors: Liu Kuang-Ting , Chang Yueh-Ching , Lin Yu-Chieh , Chang Junn-Liang
Published: June 2024

Introduction and importance:

Hepatocellular carcinoma (HCC) is a highly malignant primary hepatic tumor. However, extrahepatic metastatic sites of HCC with post-therapy dissemination of metastases mimicking primary soft tissue sarcomas with rib metastases are extremely rare.

Case presentation:

The authors report a unique case of hepatitis B virus (HBV)-positive HCC with bilateral lung involvement and widespread right-flank soft tissue and rib metastases. The pathological diagnosis after surgical resection confirmed extrahepatic HCC metastasis. Subsequently, adjuvant-targeted and immune-checkpoint inhibitor therapies were still initiated.

Clinical discussion:

Extrahepatic HCC metastasis, which initially presents at distant sites, is uncommon. HCC commonly metastasizes to the lungs, bones, lymph nodes, kidneys, adrenal glands, and peritoneum/omentum. HCC with aggressive post-scheduled adjuvant therapy to the lungs and hypochondriac soft tissue with rib metastasis is very rare and has a poor prognosis.

Conclusion:

Although most patients with HCC have disseminated extrahepatic metastases, primary HCC should still be treated. Thus, a review of the history and imaging, histopathology, and immunohistochemical findings is crucial for the definite and differential diagnosis of this tumor.
Unmet need for heart transplantation in Africa
Authors: Femi-Lawal Victor O. , Anyinkeng Achanga Bill-Smith , Effiom Victory B.
Published: June 2024

Heart transplantation is a critical treatment option for end-stage heart failure patients, offering a lifeline for those with severe cardiac conditions. However, in Africa, the unmet need for heart transplantation is a significant issue that poses challenges to the healthcare system and patient outcomes. Africa faces multiple barriers to heart transplantation, including limited infrastructure, a shortage of skilled healthcare professionals, a lack of funding, and inadequate organ donation systems. These challenges result in a considerable gap between the demand for heart transplants and the available resources to meet this need. As a result, many patients in Africa do not have access to life-saving heart transplantation procedures, leading to high mortality rates among those awaiting transplants. Addressing the unmet need for heart transplantation in Africa requires a multifaceted approach. The authors recommend that Africa as a continent build up a heart transplantation workforce involving a multidisciplinary team that consists of transplant surgeons, transplant physicians, nurses, anesthetists, pharmacists, etc. Heart transplant education and training programs should be well-constructed to ensure the delivery of safe and effective transplantation services. International collaborations have proven to be effective and should be encouraged between African institutions and transplant centers worldwide to facilitate knowledge transfer. Foreign and local organizations should promote public awareness about organ donation to address the myths about heart transplantation and promote heart donation. With these, African countries can improve access to heart transplantation, enhance patient outcomes, save lives in the region, and ultimately reduce the mortality rate in Africa.
Esophageal chemical burns as a risk factor for esophageal malignancies: in-silico analyses – experimental research
Authors: Khosravani Hengameh , Ataee Disfani Reza , Farhadi Bahar , Tohidian Mobina , Garrosi Lida , Shirvani Proushat , Zabihi Mohammad Reza , Akhoondian Mohammad , Norouzkhani Narges , Farzan Ramyar
Published: June 2024

Introduction:

Esophageal chemical burns often occur through accidental or intentional oral consumption of chemical agents and lead to severe complications such as esophageal stricture, acute perforation, and even death. Esophageal squamous cell carcinoma is a squamous epithelium tumor that lines the normal esophagus. Additionally, adenocarcinomas are tumors located at the interface between the distal esophagus and the proximal gastric and divided into esophageal adenocarcinoma and gastric-cardia adenocarcinoma. Various conditions, such as chemical burns, are considered risk factors in the disease’s pathogenesis. In the in-silico study, the authors aim to present the relationship between chemical burns and esophageal cancer by analyzing bioinformatics genetic data.

Methods:

The proper gene set was extracted using the ‘GEO’ database. The string web tool was utilized to form the gene-interaction network. Gephi and Cytoscape software were applied to achieve network analysis.

Results:

According to in-silico data, 26 genes, including NCAPH, DLGAP5, CCNB1, KIF11, KIAA0101, CDCA5, BIRC5, NUF2, BUB1B, RRM2, TTK, CDC20, NUSAP1, CCNB2, CCNA2, MELK, TPX2, PRC1, KIF4A, CENPF, TOP2A, CDK1, ASPM, CEP55, BUB1, KIF20A were extracted that can be regarded as the most critical shared genes between chemical burns and esophageal cancer.

Conclusion:

In sum, esophageal chemical burns can be related to the occurrence of esophageal cancer. Moreover, esophageal chemical burn is an external factor that upregulates present genes and can be regarded as a worsening prognosis or risk factor for esophageal cancer.
Development of a Single-Visit Protocol for the Management of Pregnancy of Unknown Location Following In Vitro Fertilization: A Retrospective Study
Authors: Dooley W. M. , de Braud L. V. , Wong M. , Platts S. , Ross J. A. , Jurkovic D.
Published: June 2024

(Abstracted from Hum Reprod 2024;39(3):509–515)

Pregnancy of unknown location (PUL) refers to a positive pregnancy test that cannot be visualized on transvaginal ultrasound. No medical intervention should be initiated without a clear diagnosis in PUL, despite the term “pregnancy of unknown location” often being used synonymously with suspected ectopic pregnancy.
Trends in HIV testing and HIV stage at diagnosis among people newly diagnosed with HIV
Authors: King Jonathan M. , Dobbins Timothy , Keen Phillip , Cornelisse Vincent J. , Stoové Mark , Nigro Steven J. , Asselin Jason , Higgins Nasra , Mao Limin , Aung Htein Linn , Petoumenos Kathy , McGregor Skye
Published: June 2024

Objective:

To identify groups more likely to be referred for HIV testing because of symptomatic presentation rather than as part of asymptomatic screening.

Design:

A retrospective analysis of Australian National HIV Registry (NHR) surveillance data including sociodemographic and clinical data, as well as reasons for HIV test.

Methods:

Using notification records from 2017 to 2022, we summarised reasons for testing leading to an HIV diagnosis. Reasons for testing were combined with clinical status at diagnosis to derive HIV testing categories: testing while symptomatic; asymptomatic HIV screening; seroconversion; and other test reason. We stratified these categories by stage of HIV at diagnosis with late-stage HIV defined as a CD4+ cell count <350 cells/μl at time of diagnosis.

Results:

Among 4134 HIV notifications with at least one reason for testing recorded, STI screening was the predominant reason for test referral (38%), followed by HIV indicative symptoms (31%), and risk behaviour (13%). By testing category, people aged 50 years or older (24%), people with HIV attributed to heterosexual sex (21%), people born in sub-Saharan Africa (19%), and women (17%) had lower levels of asymptomatic screening. More late-stage HIV diagnoses resulted from testing while symptomatic (58%) compared with asymptomatic screening (25%).

Conclusions:

Older people and heterosexuals may not access HIV focused healthcare where HIV screening is routinely offered. Instead, HIV testing opportunities may arise in other settings. By normalising HIV testing and offering low-cost HIV screening in a range of settings, it may be possible to facilitate earlier HIV diagnoses, better health outcomes, and reduced onward transmission.
A Mixed Methods Evaluation of Pharmacists' Readiness to Provide Long-Acting Injectable HIV Pre-exposure Prophylaxis in California
Authors: Beltran Raiza M. , Hunter Lauren A. , Packel Laura J. , De Martini Loriann , Holloway Ian W. , Dong Betty J. , Lam Jerika , McCoy Sandra I. , Ochoa Ayako Miyashita
Published: June 2024

Background:

Pre-exposure prophylaxis (PrEP) uptake remains low among people who could benefit, some of whom may prefer alternatives to oral PrEP, such as long-acting injectable pre-exposure prophylaxis (LAI-PrEP). We evaluated the potential for LAI-PrEP provision in pharmacies through a mixed methods study of pharmacists in California, where Senate Bill 159 enables pharmacists to independently provide oral PrEP.

Methods:

In 2022–2023, we conducted an online cross-sectional survey of California pharmacists and pharmacy students (n = 919) and in-depth interviews with pharmacists (n = 30), both of which included modules assessing attitudes about PrEP provision. Using log-binomial regression, we estimated prevalence ratios (PRs) comparing survey participants' willingness to provide LAI-PrEP by pharmacy- and individual-level characteristics. Qualitative interview data were analyzed using Rapid Qualitative Analysis to identify factors that may affect pharmacists' provision of LAI-PrEP.

Results:

Half of the survey participants (53%) indicated that they would be willing to administer LAI-PrEP using gluteal injection in their pharmacy. Willingness was higher among participants who worked in pharmacies that provided vaccinations or other injections (56% vs. 46%; PR: 1.2; 95% confidence interval: 1.0–1.4) and/or oral PrEP under Senate Bill 159 (65% vs. 51%; PR: 1.3; 95% confidence interval: 1.1–1.5) than among participants whose pharmacies did not. Interviewed participants reported barriers to LAI-PrEP provision, including the need for increased training and staffing, a private room for gluteal injections, better medication access, and payment for services.

Conclusion:

Pharmacies offer a promising setting for increased LAI-PrEP access. However, pharmacists may require additional training, resources, and policy changes to make implementation feasible.
Immune Activation Is Associated With Neurocognitive Performance in Ugandan Adolescents Living With HIV
Authors: Dirajlal-Fargo Sahera , Sattar Abdus , Strah Monika , Karungi Christine , Gumikiriza-Onoria Joy Louise , Santoro Anthony F. , Kirsch Courtney , Nanteza Angel , Ferraris Christopher M. , Tsapalas Daphne , Asiedu Nana , Funderburg Nicholas , Musiime Victor , McComsey Grace A. , Robbins Reuben N.
Published: June 2024

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tablet-based neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4+ and CD8+) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13–16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7–11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV (P = 0.05) and significantly worse on tests of executive functioning and delayed recall (P's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P = 0.04), attention, processing speed, and motor speed (r = 0.2–0.3, P ≤ 0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r = 0.2–0.4, P ≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI: −0.55 to −0.07, P = 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting.
Analysis of Cephalometric Differences of the Midface and Upper Face in Males and Females: A Radiographic Study
Authors: Shi Lucy L. , Lacey Marcus , Teixeira Jeffrey , Hendershot Kelly , Hohman Marc , Kidwai Sarah , Flaherty A.J. , Nuara Michael J.
Published: June 2024

Gender affirmation facial surgery (GAFS) is an important component in treating gender dysphoria among transgender individuals by addressing gender incongruence of the face. There is a paucity of literature describing objective characterizations of the anatomic differences between male and female faces. In this study, cephalometric measurements were taken on routine CT imaging performed on cisgender patients between 2017 and 2020. Specifically defined cephalometric landmarks of the upper and midface were measured and compared between male and female cohorts. Thirty-eight patients, 19 male and 19 female, were identified for this study. Significant differences were identified in the frontal prominence, orbital size, malar height, bizygomatic width, nose, and upper lip, with moderate rates of specificity for each gender. Some important ratios are also presented. Differences in the malar region and the orbit highlight the importance of these areas as a point of focus for GAFS. These cephalometric findings provide objective evidence and parameters for perceived anatomic differences in male and female faces. In addition, they help both corroborate current surgical techniques as well as guide future approaches to GAFS.
Less Is More
Authors: Magnotti Louis J. , Bhogadi Sai Krishna , Anand Tanya , Stewart Collin , Colosimo Christina , Spencer Audrey L. , Nelson Adam , Joseph Bellal
Published: June 2024

Objective:

This study aims to examine the relationship between procedural volume and annual trauma volume (ATV) of ACS Level I trauma centers (TC).

Background:

Although ATV is a hard criterion for TC verification, importance of procedural interventions as a potential quality indicator is understudied.

Methods:

Patients managed at ACS level I TCs were identified from ACS-TQIP 2017–2021. TCs were identified using facility keys and stratified into quartiles based on ATV into low, low-medium, medium-high, and high volume. TCs were also stratified into tertiles [low (LV), medium (MV), high (HV)] based on procedural volume by assessing annual number of laparotomies, thoracotomies, craniotomies/craniectomies, angioembolizations, vascular repairs, and long bone fixations performed at each center. The Cohen κ statistic was used to assess concordance between ATV and procedural volume.

Results:

A total of 182 Level I TCs were identified: 76 low, 47 low-medium, 35 high-medium, and 24 high volume. Long bone fixation, laparotomy, and craniotomy/craniectomy were the most performed procedures with a median of 65, 59, and 46 cases/center/year, respectively. Overall, 31% of HV laparotomy centers, 31% of HV thoracotomy centers, 22% of HV craniotomy/craniectomy centers, 22% of HV vascular repair centers, 32% of HV long bone fixation centers, and 33% of HV angioembolization centers contributed to the overall number of low-medium and low-volume TCs. The Cohen κ statistic demonstrated poor concordance between ATV and procedural volumes for all procedures (overall procedural volume—κ=0.378, laparotomy—κ=0.270, thoracotomy—κ=0.202, craniotomy/craniectomy—κ=0.394, vascular repair—κ=0.298, long bone fixation—κ=0.277, angioembolization—κ=0.286).

Conclusions:

ATV does not reflect the procedural interventions performed. Combination of procedural and ATV may provide a more accurate picture of the clinical experience at any given TC.

Level of Evidence:

Level III.
Repeated COVID-19 Vaccination Drives Memory T- and B-cell Responses in Kidney Transplant Recipients: Results From a Multicenter Randomized Controlled Trial
Authors: Malahe S. Reshwan K. , den Hartog Yvette , Rietdijk Wim J. R. , van Baarle Debbie , de Kuiper Ronella , Reijerkerk Derek , Ras Alicia M. , Geers Daryl , Diavatopoulos Dimitri A. , Messchendorp A. Lianne , van der Molen Renate G. , Imhof Céline , Frölke Sophie C. , Bemelman Frederike J. , Gansevoort Ron T. , Hilbrands Luuk B. , Sanders Jan-Stephan F. , GeurtsvanKessel Corine H. , Kho Marcia M. L. , de Vries Rory D. , Reinders Marlies E. J. , Baan Carla C. ,   On behalf of RECOVAC Consortium
Published: June 2024

Background.

Insight into cellular immune responses to COVID-19 vaccinations is crucial for optimizing booster programs in kidney transplant recipients (KTRs).

Methods.

In an immunologic substudy of a multicenter randomized controlled trial (NCT05030974) investigating different repeated vaccination strategies in KTR who showed poor serological responses after 2 or 3 doses of an messenger RNA (mRNA)-based vaccine, we compared SARS-CoV-2-specific interleukin-21 memory T-cell and B-cell responses by enzyme-linked immunosorbent spot (ELISpot) assays and serum IgG antibody levels. Patients were randomized to receive: a single dose of mRNA-1273 (100 μg, n = 25), a double dose of mRNA-1273 (2 × 100 μg, n = 25), or a single dose of adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein (Ad26.COV2.S) (n = 25). In parallel, we also examined responses in 50 KTR receiving 100 μg mRNA-1273, randomized to continue (n = 25) or discontinue (n = 25) mycophenolate mofetil/mycophenolic acid. As a reference, the data were compared with KTR who received 2 primary mRNA-1273 vaccinations.

Results.

Repeated vaccination increased the seroconversion rate from 21% to 66% in all patients, which was strongly associated with enhanced levels of SARS-CoV-2-specific interleukin-21 memory T cells (odd ratio, 3.84 [1.89-7.78]; P < 0.001) and B cells (odd ratio, 35.93 [6.94-186.04]; P < 0.001). There were no significant differences observed in these responses among various vaccination strategies. In contrast to KTR vaccinated with 2 primary vaccinations, the number of antigen-specific memory B cells demonstrated potential for classifying seroconversion after repeated vaccination (area under the curve, 0.64; 95% confidence interval, 0.37-0.90; P = 0.26 and area under the curve, 0.95; confidence interval, 0.87-0.97; P < 0.0001, respectively).

Conclusions.

Our study emphasizes the importance of virus-specific memory T- and B-cell responses for comprehensive understanding of COVID-19 vaccine efficacy among KTR.
Normative Data and Quantile Regression Analysis of the Sural-to-Radial Nerve Amplitude Ratio
Authors: Pourhamidi Kaveh
Published: June 2024

Purpose:

The aim of this study was to establish normative data for the sural-to-radial nerve amplitude ratio (SRAR) and develop a quantile regression model for individualized cutoff values.

Methods:

A cohort of 68 healthy individuals (36 female participants) aged 20 to 59 years was recruited. Sensory nerve conduction studies were conducted to measure sural and radial sensory nerve action potential amplitudes. Quantile regression analysis was used to determine the fifth percentile of SRAR after adjusting for age, sex, and other demographic variables.

Results:

This study found significant differences in body height and weight between the sexes, with radial sensory nerve action potential being higher in female participants. The sural-to-radial nerve amplitude ratio was negatively correlated with age (r = −0.3, p = 0.007) and showed significant sex differences. The final regression equation, SRAR = 0.519 − 0.006 × age + 0.046 × sex (1 = male, 0 = female), was developed for the fifth percentile cutoff, accounting for age and sex.

Conclusions:

This study establishes normative SRAR data and introduces a novel quantile regression approach to determine individualized cutoff values. Age and sex are critical factors for SRAR variation, necessitating tailored diagnostic criteria for neuropathy assessment. This model enhances diagnostic accuracy and potentially reduces misdiagnosis in clinical settings. Further research is recommended to validate the clinical applicability of SRAR across different types of neuropathies.
Intraoperative Neurophysiological Monitoring in Tethered Cord Syndrome Surgery: Predictive Values and Clinical Outcome
Authors: Squintani Giovanna , Basaldella Federica , Badari Andrea , Rasera Andrea , Tramontano Vincenzo , Pinna Giampietro , Moscolo Fabio , Soda Christian , Ricci Umberto , Ravenna Giorgio , Sala Francesco
Published: June 2024

Introduction:

“Tethered cord syndrome” (TCS) refers to a congenital abnormality associated with neurological signs and symptoms. The aim of surgery is to prevent or arrest their progression. This study reports a retrospective case series of tethered cord syndrome surgeries, supported by intraoperative neurophysiological monitoring.

Methods:

The case series comprises 50 surgeries for tethered cord syndrome in which multimodal intraoperative neurophysiological monitoring was performed using motor evoked potentials (transcranial motor evoked potentials [TcMEPs]), tibial nerve somatosensory evoked potentials (TNSEPs), and pudendal-anal reflex (PAR). The intraoperative neurophysiological monitoring results are reported and correlated with clinical outcomes.

Results:

Sensitivity, specificity, and negative predictive value were high for TcMEPs and TNSEPs, while PAR exhibited low sensitivity and positive predictive value but high specificity and negative predictive value. Fisher's exact test revealed a significant correlation between changes in TcMEPs, TNSEPs, and clinical outcome (P < 0.000 and P = 0.049 respectively), but no correlation was detected between PAR and urinary/anal function (P = 0.497).

Conclusions:

While TcMEPs and TNSEPs were found to be reliable intraoperative neurophysiological monitoring parameters during tethered cord syndrome surgery, PAR had low sensitivity and positive predictive value probably because the reflex is not directly related to bladder function and because its multisynaptic pathway may be sensitive to anesthetics. New onset muscle weakness and sensory deficits were related to postoperative changes in TcMEPs and TNSEPs, whereas changes in PAR did not predict bladder/urinary impairment. Urinary deficits may be predicted and prevented with other neurophysiological techniques, such as the bladder–anal reflex.
Are We Supporting Surgical Quality Improvement in Training and Beyond? A Qualitative Study of Surgical Trainees and Practicing Surgeons
Authors: Peters Xane D , Waddle Shelbie D , Shah Tejen , Reilly Eileen , Valek Sarah , Modla Lynn , Langenscheidt Ulrike , Pollitt Karen , Johnson Julie K , Ko Clifford Y
Published: June 2024

BACKGROUND:

We conducted a qualitative study to describe surgeon and surgical trainee perspectives of quality improvement (QI) in training and practice to elucidate how surgeons and trainees interact with barriers and leverage facilitators to learn and conduct QI.

STUDY DESIGN:

Surgeons and surgical trainees of the American College of Surgeons were recruited via email and snowball sampling to participate in focus groups. Eligible individuals were English speaking surgical trainees or practicing surgeons. We developed a semistructured focus group protocol to explore barriers and facilitators of quality training and improvement. An inductive thematic approach was used to identify actionable items.

RESULTS:

Thirty-two surgical trainees and surgeons participated in 6 focus groups. A total of 28% of participants were trainees (8 residents, 1 fellow) and 72% were practicing surgeons, representing practice settings in university, community, and Veterans Affairs hospitals in urban and suburban regions. Thematic analysis revealed that the central theme among trainees was that they lacked necessary support to effectively learn and conduct QI. Dominant subthemes included lack of formal education, insufficient time, inconsistent mentorship, and maximizing self-sufficiency to promote success. The central theme among surgeons was that effective QI initiatives require adequate resources and institutional support; however, surgeons in this study were ultimately constrained by institutional limitations. Subthemes included difficulties in data acquisition and interpretation, financial limitations, workforce and staffing challenges, misaligned stakeholder priorities, and institutional culture.

CONCLUSIONS:

This qualitative evaluation further details gaps in QI demonstrated by previous quantitative studies. There is an opportunity to address these gaps with dedicated QI training and mentorship for surgical trainees and by creating a supportive environment with ample resources for surgeons.
Modelling and simulation of the cholesteric Landau-de Gennes model
Authors: Hicks Andrew L. , Walker Shawn W.
Published: June 2024

This paper discusses modelling and numerical issues in the simulation of the Landau-de Gennes (LdG) model of nematic liquid crystals (LCs) with cholesteric effects. We propose a fully implicit, (weighted)

L
2

gradient flow for computing energy minimizers of the LdG model, and note a time-step restriction for the flow to be energy decreasing. Furthermore, we give a mesh size restriction, for finite-element discretizations, that is critical to avoid spurious numerical artifacts in discrete minimizers, particularly when simulating cholesteric LCs that exhibit ‘twist.’ Furthermore, we perform a computational exploration of the model and present several numerical simulations in three dimensions, on both slab geometries and spherical shells, with our finite-element method. The simulations are consistent with experiments, illustrate the richness of the cholesteric model, and demonstrate the importance of the mesh size restriction.
Astrocyte-Derived Exosomes Regulate Sperm miR-34c Levels to Mediate the Transgenerational Effects of Paternal Chronic Social Instability Stress
Authors: Champroux Alexandre , Sadat-Shirazi Mitra , Chen Xuan , Hacker Jonathan , Yang Yongjie , Feig Larry A.
Published: June 2024

The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content that induce stress-specific phenotypes in their offspring. But how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not understood. Here we describe evidence forastrocyte-derivedexosomes (A-Exos) containing miR-34c mediating how chronic social instability (CSI) stress suppesses levels of miR-34c in sperm, which we showed previously contributes to how this stress protocol leads to both elevated anxiety and defective sociability in their female offspring and reduced sperm miR-34c in their male offspring. In particular, we found that CSI stress decreases content of miR-34c in A-Exos isolated from the prefrontal cortex and amygdala, as well as in blood of CSI-stressed males. Strikingly, miR-34c content is also reduced in A-Exos isolated from these tissues of their F1 male offspring, who also display reduced sperm miR-34c levels despite never being directly exposed to stress and transmit these stress related traits to their offspring. In addition, restoring A-Exos miR-34c content in the blood of CSI-stressed males by IV injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal a surprising role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.
Surviving Medical School During a Pandemic: Experiences of New York Medical Students During the Height of SARS-CoV-2
Authors: Knight L. M. , Seth Divya , Zuckerman David A. , Rogers Eli J. , Talukdar Zain , Holloway Robert , Gómez-Di Cesare Caroline , Henshaw Mariluz , Privitera Michael , Dowling Frank
Published: June 2024

Background

The COVID-19 pandemic dramatically altered the landscape of medical education. While patients overwhelmed hospital systems, lockdowns and social distancing recommendations took priority, and medical education was pushed online. Early in 2020, New York State (NYS) was hit especially hard by COVID-19.

Objective

This study sought to understand the effect of the COVID-19 pandemic on medical students well-being and education.

Methods

NYS medical students responded to a six-question survey during April and May 2020. Questions assessed self-reported changes in stress levels, academic performance, and board preparation efforts. Open-ended data was analyzed using a modified grounded theory approach.

Results

488 responses across 11 medical schools were included (response rate of 5.8%). Major themes included: standardized test-related stressors (23%), study-related changes (19%), education and training concerns (17%), financial stressors (12%), and additional family obligations (12%).

Second year students reported more stress/anxiety than students in other years (95.9%,p-value< 0.00001). Reported stress/anxiety, effects on exam preparation, and anticipated academic effect varied by geographics.

Conclusions

While all NYS medical students reported being greatly affected, those closest to the NY City pandemic epi-center and closest to taking the Step 1 exam were the most distressed. Lack of flexibility of the medical education system during this public health emergency contributed to worsened student well-being. It is time to make plans for supporting the long-term mental health needs of these physicians-in-training and to examine ways the academic medical community can better adapt to the needs of students affected by a large public health emergency in the future.
RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events
Authors: Guan Liying , Voora Deepak , Myers Rachel , Del Carpio-Cano Fabiola , Rao A. Koneti
Published: June 2024

Background

Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown.

Objectives

To understand the regulation of RUNX1 and its target genes by RUNX1 isoforms.

Methods

We performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD).

Results

In chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5Aand others) differentially in HEL cells. In platelets RUNX1B transcripts (by RNAseq) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively withF13A1, PCTP, PDE5A, RAB1B, and others, and negatively withMYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targetsF13A1andRAB31associated with acute events.

Conclusions

RUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner and this associates with acute events in CVD.

Scientific category

Platelets

Essentials

RUNX1 is expressed from 2 promoters (P1 and P2) to yield isoforms RUNX1C and RUNX1B.

RUNX1B and RUNX1C regulate RUNX1 and target genes differentially in megakaryocytes/platelets.

In platelets RUNX1B and RUNX1C expression is inversely related and ticagrelor increases RUNX1C

RUNX1 target gene (F13A1, RAB31) expression in blood is associated with death or MI in cardiac disease.
The bacterial Bmt methionine synthase is involved in lag phase shortening
Authors: Narváez-Barragán Delia A. , Sperfeld Martin , Segev Einat
Published: June 2024

Bacteria can shorten their lag phase by utilizing methyl groups from compounds such as dimethylsulfoniopropionate (DMSP). These methyl groups are then incorporated into cellular building blocks via the methionine cycle. However, the specific contribution of bacterial methionine synthesis, which is critical for assimilating and incorporating methyl groups, remains unclear.

In this study, we employed transcriptomics, genetic manipulation and biochemical assays to explore the involvement of methionine synthesis in lag phase shortening using the model marine bacteriumPhaeobacter inhibens. We mapped the expression profiles of the MetH-like methionine synthase components—an enzyme complex that is encoded by three genes—in response to DMSP during the lag phase. Our findings revealed transcriptional decoupling of the three genes. The deletion of the homocysteine-binding component of the MetH-like complex, namelybmt, disrupted lag phase shortening in response to DMSP. Through heterologous expression of thebmtgene product, we show that the individual Bmt enzyme produces methionine by directly demethylating DMSP and betainein vitro. These findings reveal a metabolic route that was not previously described in marine bacteria. Since Bmt does not require tetrahydrofolate or cobalamin as co-factors for methionine synthesis, its potential to act alone as a demethylase and a methionine synthase represents a cost-effective metabolic shortcut for methyl group assimilation, which could be specifically beneficial under limiting conditions. Indeed, we show that under stress conditions, Bmt allows cells to shorten their lag phase in response to DMSP.

This study enhances our understanding of the enzymatic mechanisms underlying bacterial lag phase shortening, revealing microbial adaptation strategies in response to environmental conditions.
Distribution of informal caregiving for older adults living with or at risk of cognitive decline within and beyond family in rural South Africa
Authors: Matina Sostina S , Manderson Lenore , Brear Michelle , Rusere Farirai , Gómez-Olivé F. Xavier , Kahn Kathleen , Harling Guy
Published: June 2024

Objectives

Aging populations in rural areas of low and middle-income countries will increasingly need care. However, formal support is severely limited and adult children are frequently unavailable due to morbidity, early mortality, employment and migration. We aimed to describe how care is shared within and between households for older adults in a rural South African setting.

Methods

We conducted quantitative interviews with 1012 household members and non-household caregivers of 106 older adults living with or at risk of cognitive decline in rural Mpumalanga, South Africa. Using descriptive statistics and regression analysis, we described how care is shared, with particular attention to generational patterns of care.

Results

Informal care for older persons was spread among family, friends, and neighbours, with minimal paid support. This care was mostly provided by female relatives one or two generations younger than the recipient, and unemployed. However, a smaller number of paid caregivers, also mostly female, provided the most intensive care. Spouses commonly took on the role of primary caregiver for their partner.

Discussion

In our study, care mainly came from household members due to close family ties and practical considerations, with support from outside the household. This reflects shared history, reciprocal relationships, and easy access to care tasks within the household. A deeper understanding of how informal care for older adults is shared in low- and middle-income countries is essential for developing targeted interventions.
Investigating the relationship between the immune response and the severity of COVID-19: a large-cohort retrospective study
Authors: Margiotta Riccardo Giuseppe , Sozio Emanuela , Del Ben Fabio , Beltrami Antonio Paolo , Cesselli Daniela , Fabris Martina , Curcio Francesco , Tascini Carlo , Sanguinetti Guido
Published: June 2024

The COVID-19 pandemic has left an indelible mark globally, presenting numerous challenges to public health. This crisis, while disruptive and impactful, has provided a unique opportunity to gather precious clinical data extensively. In this observational, case-control study, we utilized data collected at the Azienda Sanitaria Universitaria Friuli Centrale, Italy, to comprehensively characterize the immuno-inflammatory features in COVID-19 patients. Specifically, we employed multicolor flow cytometry, cytokine assays, and inflammatory biomarkers to elucidate the interplay between the infectious agent and the host’s immune status. We characterized immuno-inflammatory profiles within the first 72 hours of hospital admission, stratified by age, disease severity, and time elapsed since symptom onset. Our findings indicate that patients admitted to the hospital shortly after symptom onset exhibit a distinct pattern compared to those who arrive later, characterized by a more active immune response and heightened cytokine activity, but lower markers of tissue damage. We used univariate and multivariate logistic regression models to identify informative markers for outcome severity. Predictors incorporating the immuno-inflammatory features significantly outperformed standard baselines, identifying up to 59% of patients with positive outcomes while maintaining a false omission rate as low as 4%. Overall, our study sheds light on the immuno-inflammatory aspects observed in COVID-19 patients prior to vaccination, providing insights for guiding the clinical management of first-time infections by a novel virus.
An Algorithm to Predict the Need for Magnetic Resonance Imaging to Support Disease Monitoring in Multiple Sclerosis
Authors: Robinette Michael S. , Gray-Roncal Karla , Fitzgerald Kathryn C. , Ferryman Kadija , Overby Taylor Casey , Scott John , Sotirchos Elias S. , Calabresi Peter A. , Mowry Ellen M. , Gray-Roncal William
Published: June 2024

People with multiple sclerosis (MS), a chronic neurologic disease, typically undergo brain magnetic resonance imaging (MRI) to assess for new disease activity or to evaluate response to disease-modifying therapy. The required frequency of these imaging studies has not yet been determined, and clinicians rely on expert panel recommendations or intuition to select the interval length for their patients. These former recommendations are often broad and lack the incorporation of individualized information (i.e., age, presence of recent disease activity, type of disease modifying therapy) into the synthesis of their assessment. We developed an algorithm that can predict new disease activity (i.e., lesions) on the next MRI scan. Multiple data sources from the electronic health records of 1045 patients were used to train and test the algorithm which resulted in an accurate solution with an area under the curve (AUC) of 0.8 that minimizes missed lesions while accurately identifying two-thirds of patients as not having a new lesion in subsequent MRI. We believe that this algorithm can be developed into a clinical decision support tool as input into a clinician-patient assessment of the appropriate interval length between MRIs for a specific patient.