bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Qigong Mawangdui Guidance can improve pelvic floor muscle function and quality of life in females with stress urinary incontinence: A randomized controlled trial pilot study
Authors: Xu Ming , Zhang Xu , Zhuo Yue , Wu Wanrong , Liu Qiong , Qin Shuang , Long Zhuan , Ai Kun , Li Ya , Zhang Hong
Published: April 2024

Background:

Urinary incontinence (UI) is a great problem of public health, especially for women’s quality of life. UI afflicts at least 21.6% of the global population, and more than half of the UI is related to female stress urinary incontinence (SUI). Mawangdui Guidance plays an important role in preventing diseases and maintaining health.

Methods:

Sixty female patients with SUI were randomly divided into a control group (n = 30) and an experimental group (n = 30). Patients in both groups were treated with basic rehabilitation therapy under the guidance of rehabilitation therapists who were trained in Mawangdui Guidance, based on the former, the experimental group was taught to exercise Mawangdui Guidance(including selected movements: “Qishi,” “Longdeng,” “Chishi,” and “Yinyao”), while the control group performed Kegel exercise with a procedure of 20 min, six times per week for 6 weeks. The function was mainly evaluated by the 1 h pad-test, incontinence quality of life questionnaire (I-QOL), and international consultation on incontinence questionnaire urinary incontinence short form (ICI-Q-SF). In addition, evaluation of pelvic floor muscle function was also included in our assessment.

Results:

The leakage of urine in the 1 h pad-test was significantly decreased in both two groups after treatment (P < .05), and the urine leakage in the experimental group was significantly less than that in the control group (P < .05). The muscle strength of type I and II muscle fibers of the pelvic floor, intravaginal pressure, and I-QOL score in both two groups were increased after treatment; moreover, the experimental group was more significant than the control group (P <.05). The fatigue degree of type I and type II muscle fibers of the pelvic floor, and the ICI-Q-SF score in both groups were significantly improved after treatment (P < .05); however, there were no differences between these two groups. The total effective rate of the experimental group was 90.00%, and 76.67% in the control group (P <.05).

Conclusion:

Mawangdui Guidance can effectively improve the function of pelvic floor muscle, improve the ability of urine storage and control, and alleviate the symptoms of female patients with SUI. However, the international research on Mawangdui Guidance is very limited, and more in-depth research is needed.
Trends in hospital admissions and prescribing due to diseases of the digestive system in England and Wales between 1999 and 2019: An ecological study
Authors: Alwafi Hassan , Alsharif Alaa
Published: April 2024

This study aimed to investigate the trends in diseases of the digestive system hospital admissions (DDSHA) in England and Wales between (1999–2019). Secondary objectives were to investigate the type of admission and medication prescribing related to the digestive system in England. This is an ecological study using data from the Hospital Episode Statistics (HES) database and the Patient Episode Database between April 1999 and March 2019. The rate of hospital admissions with 95% confidence intervals (CIs) was calculated by dividing the number of DDSHA by the mid-year population. The trend in hospital admissions was assessed using a Poisson model. Overall, the rate of DDSHA rose by 84.2% (from 2231.27 [95% CI 2227.26–2235.28] in 1999 to 4109.33 [95% CI 4104.29–4114.38] in 2019 per 100,000 persons, trend test, P < .001). The most remarkable rise in hospital admission was seen in liver diseases, followed by other diseases of intestines with 1.85-fold, and 1.59-fold, respectively. Between 2004 and 2019, the overall prescribing rate for medications related to the gastrointestinal system increased by 74.6%, and stoma care related medications prescribing rate increased by 2.25-fold, followed by drugs affecting intestinal secretions and antisecretory drugs and mucosal protectants. There was an increase in hospital admission rate due to GI diseases in the United Kingdom (UK) by 84.2% from 1999 to 2019. The most remarkable rise in the rate of hospital admissions was seen in diseases of the liver and intestine.
Epidemiology of congenital malformations of the external ear in Hunan Province, China, from 2016 to 2020
Authors: Zhou Xu , Fang Junqun , Wang Xiaoli , Kuang Haiyan , He Jian , Wang Aihua , Hua Xinjun , Zeng Xiu , Zeng Shuxian
Published: April 2024

To describe the epidemiology of congenital malformations of the external ear (CMEE). Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016 to 2020. The prevalence of CMEEs is defined as the number of cases per 1000 fetuses (births and deaths at 28 weeks of gestation and beyond) (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ2

trend
) were used to determine trends in prevalence by year. P < .05 was considered statistically significant. Crude odds ratios (ORs) were calculated to examine the association of sex, residence, and maternal age with CMEEs. Our study included 847,755 fetuses, and 14,459 birth defects were identified, including 1227 CMEEs (accounted for 8.49% of birth defects). The prevalences of birth defects and CMEEs were 17.06‰ (95%CI: 16.78–17.33) and 1.45‰ (95%CI: 1.37–1.53), respectively. A total of 185 microtia-anotias were identified, accounting for 15.08% of CMEEs, with a prevalence of 0.22‰ (95%CI: 0.19–0.25). And 1042 other CMEEs were identified, accounting for 84.92% of CMEEs. From 2016 to 2020, the prevalences of birth defects were 18.20‰, 18.00‰, 16.31‰, 16.03‰, and 16.47‰, respectively, showing a downward trend (χ2
trend =8.45, P < .01); the prevalences of CMEEs were 1.19‰, 1.62‰, 1.80‰, 1.21‰, and 1.35‰, respectively, with no significant trend (χ2
trend =0.09, P = .77). CMEEs were more common in males than females (1.60‰ vs 1.27‰, OR = 1.26, 95%CI: 1.12–1.41), in urban areas than in rural areas (1.77‰ vs 1.23‰, OR = 1.45, 95%CI: 1.29–1.62). The prevalences of CMEEs for maternal age < 20, 20–24, 25–29, 30–34, and ≥ 35 were 1.75‰, 1.27‰, 1.44‰, 1.47‰, and 1.58‰, respectively, with no significant difference (P > .05, reference: 25–29). Most CMEEs were diagnosed by clinical examinations (92.34%), and most CMEEs were diagnosed postpartum (within 7 days) (96.25%). In summary, we have presented the epidemiology of CMEEs in Hunan Province, China. CMEEs were more common in males than females, in urban areas than rural areas, whereas there was no significant difference in prevalence of CMEEs by maternal age. We inferred that CMEEs may be mainly related to genetics, and the mechanism needs to be examined in the future.
Frequency of missed doses and its effects on the regulation of glucose levels in patients with type 2 diabetes: A retrospective analysis
Authors: Shiomi Megumi , Takada Tesshu , Otori Katsuya , Shibuya Kiyoshi
Published: April 2024

This study aimed to investigate the association between medication adherence to oral hypoglycemic agents (OHAs) and HbA1c levels in patients with type 2 diabetes mellitus (T2DM) for more than 48 weeks, as well as the factors affecting long-term adherence to OHAs. This retrospective study included 83 patients who had been receiving OHAs for T2DM for ≥48 weeks. Medication adherence values (MAVs) were calculated using the following formula: (total prescription days − prescription days of OHAs brought at admission)/(days from the initiation of OHAs to hospitalization). We assessed the association between HbA1c and MAVs using the Jonckheere–Terpstra test. Furthermore, we examined the association between patient- and medication-related factors and MAVs affecting HbA1c levels. Based on the results, MAVs were categorized as MAV ≤0.86 and MAV >0.86, and factors affecting MAVs were analyzed. Logistic regression analysis revealed that the total number of medications, the number of nonhypoglycemic agents, and a family history of diabetes were independent determinants of MAV ≤0.86 (P < .05). Multiple regression analyses indicated that the number of dosages per day and the timing of OHA administration at lunch were independent determinants of lower MAVs (P < .05). Our findings suggest that poor medication adherence is associated with elevated HbA1c levels in T2DM patients. Independent factors contributing to poor adherence include a lower number of prescribed medications, fewer nonhypoglycemic agents, no family history, a higher daily dosage frequency, and the administration of OHAs at lunch.
A unicentric center, multicenter, and mixed-type Castleman disease: Three case reports and a review of the literature
Authors: Xu Yang , Shao Shuai , Kang HaoNan , Xu ZhaoHui , Wen GuoYi , Shan Yan , Gong ZeZhong , Al-Sharabi Abdulkarem , Qu BoXin , Ren YanYing , Zhang Fan , Guan JinMing , Chen Xin
Published: April 2024

Rationale:

Due to the lack of specificity symptoms and site of onset of castleman disease (CD), it is difficult to diagnose and poses unique challenges for both patients and clinicians, leading to confusion in diagnosis and delays in treatment. To enhance understanding, we present 3 cases of CD treated at our hospital, including a single-center, multicenter, and mixed-type CD.

Patient concerns:

Case 1: A 53-year-old female patient was admitted with a chief complaint of “abdominal pain and fever for 10 days.” Marked enlargement of inguinal lymph nodes on both sides was observed. Case 2: A 58-year-old female patient was admitted with the main complaint of “discovering a left lower abdominal mass during a routine checkup for the past 10 days.” Upon deep palpation, a palpable mass of approximately 5.0 * 3.0 cm was identified in the left lower abdomen. Case 3: A 40-year-old male patient was admitted with the main complaint of “progressive right upper abdominal and lumbar back pain for over 6 months.” Computed tomography examination revealed multiple nodular soft tissue masses between the abdominal aorta and inferior vena cava, with the largest measuring 5.0 * 4.0 cm.

Diagnoses:

Based on the immunohistochemical results, the diagnoses for the 3 patients are as follows: Case 1: Multicentric Castleman’s Disease (Mixed Type). Case 2: Pelvic Retroperitoneal Castleman Disease (Hyaline Vascular Type). Case 3: Castleman Disease Multicentric Type.

Intervention:

Case 1: cyclophosphamide 0.6–1 g + vincristine 2 mg + methylprednisolone 50 mg/5 days. Cyclophosphamide 1 g + prednisone 30–50 mg/5 days. This alternating chemotherapy cycle is repeated every 6 months. Case 2: Laparoscopic pelvic mass excision surgery. Case 3: Surgical excision of the mass.

Outcomes:

Case 1: After a 43-month follow-up, the patient’s general symptoms have improved compared to before, but regular chemotherapy is still necessary at present. Case 2: The patient did not take any medication postoperatively, and there has been no evidence of metastasis or recurrence during the 18-month follow-up. Case 3: The patient did not take any medication, and there has been no evidence of metastasis or recurrence during the 21-month follow-up.

Lessons subsections:

The lack of specific signs on imaging studies and nonspecific blood tests increases the difficulty of diagnosis. However, tissue biopsy remains a feasible option. Therefore, we recommend conducting thorough examinations for suspected CD patients to reduce misdiagnosis and determine the CD type for effective targeted treatment.
Morphometric assessment of tibial nerve and its branches around the ankle
Authors: Kwon Jeha , Park Hong Bum , Kwon Soonwook , Rhyu Im Joo , Kim Dong Hwee
Published: April 2024

It is essential to understand the considerable variations in bifurcation patterns of the tibial nerve (TN) and its peripheral nerves at the level of the tarsal tunnel to prevent iatrogenic nerve injury during surgical nerve release or nerve block. A total of 16 ankles of 8 human cadavers were dissected to investigate the branching patterns of the TN, using 2 imaginary lines passing through the tip of the medial malleolus (MM) as reference lines. Bifurcation patterns and detailed information on the relative locations of the medial plantar, lateral plantar, medial calcaneal, and inferior calcaneal nerves to the reference lines were recorded. The most common bifurcation pattern was Type 1 in 12 ankles (75%), followed by Type 2 in 2 ankles (13%). One medial calcaneal nerve (MCN) was seen in 11 (69%) specimens and 2 MCN branches were seen in 5 (31%) specimen. 88% of the MCN branches bifurcated from the TN, whereas 6% originated from both TN and lateral plantar nerve (LPN). At the level of the tip of the MM, 2 of 7 parameters showed statistically significant difference between both sexes (P < .05). There was a statistically significant difference between left and right ankles in 2 of 7 measurements (P < .05). Further morphometric analysis of the width, distance, and angle between the TN branches and the tip of MM showed a highly variable nature of the location of the peripheral nerve branches.
A new equation for estimating low-density lipoprotein cholesterol concentration based on machine learning
Authors: Chen Lei , Rong Chen , Ma Peidu , Li Yiyang , Deng Xue , Hua Muxing
Published: April 2024

Low-density lipoprotein cholesterol (LDL-C) is a crucial marker of cardiovascular system damage. In the Chinese population, the estimation of LDL-C concentration by Friedewald, Martin-Hopkins or Sampson equations is not accurate. The aim of this study was to develop a group of new equations for calculating LDL-C concentration using machine learning techniques and to evaluate their efficacy. A total of 182,901 patient samples were collected with standard lipid panel measurements. These samples were collated and randomly divided into a training set and a test set. In the training set, a new equation was constructed using polynomial ridge-regression and compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations in the test set. Subsequently, an additional set of 17,285 patient samples were collected to evaluate the performance of the new equation in clinical practice. The new equation, a ternary cubic equation, was accurate and easy to use, with a goodness-of-fit R2 of 0.9815 and an uncertainty MSE of 37.4250 on the testing set. The difference between the calculated value by the new equation and the measured value of LDL-C was small (0.0424 ± 5.1161 vs Friedewald equation: −13.3647 ± 17.9198, vs Martin/Hopkins and extended Martin/Hopkins equation: −6.4737 ± 8.1036, vs Sampson equation: −8.9252 ± 12.6522, P < .001). It could accurately calculate LDL-C concentration even at high triglyceride and low LDL-C. Furthermore, the new equation could also precisely calculate LDL-C concentration in actual clinical use (R2 = 0.9780, MSE = 24.8482). The new equation developed in this study can accurately calculate LDL-C concentration within the full concentration range of triglyceride and LDL-C, and can serve as a supplement to the direct determination of LDL-C concentration for the prevention, treatment, evaluation, and monitoring of atherosclerotic diseases, compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations.
Feasibility, safety and oncological short-term outcome of laparoscopic pancreaticoduodenectomy for periampullary cancer: Findings from a large sample from Vietnam
Authors: Pham Hai Minh , Le Quan Anh Tuan , Nguyen Bac Hoang
Published: April 2024

Laparoscopic pancreaticoduodenectomy (LPD) is an alternative to open pancreaticoduodenectomy (OPD) for treatment of periampullary cancer in selected patients. However, this is a difficult procedure with a high complication rate. We conducted a prospective cohort study of 85 patients with suspected periampullary cancer who underwent LPD from February 2017 to January 2022 at University Medical Center at Ho Chi Minh City, Vietnam. Among these, 15 patients were excluded from the data analysis because of benign disease confirmed by postoperative pathological examination. Among 70 patients, the mean age was 58.9 ± 8.9 years old and 51.4% were female. The conversion rate to open surgery was 7.1% (n = 5). Among those underwent LPD, the mean operating time and estimated blood loss were 509 ± 94 minutes and 267 ± 102 mL, respectively. The median length of hospital stay was 8 days, interquartile range (IQR) 7–12 days. The percentage of cumulative morbidity, pancreatic fistula and major complication was 35.4%, 12.3%, and 13.8%, respectively. The median of comprehensive complication index (CCI) was 26.2 (IQR 20.9–29.6). Three patients required reoperation due to severe pancreatic fistula (n = 2) and necrotizing pancreatitis (n = 1). There was no death after ninety-day. The average number of harvested lymph nodes was 16.6 ± 5.1. The percentage of R0 resection was 100%. With properly selected patients, LPD can be a feasible, safe and effective approach with acceptable short-term outcomes.
Clinical and genetic analysis of a case of Gitelman syndrome accompanied with Graves disease and adrenocortical adenoma: A case report
Authors: Qiao Yan , Zhao Jinghong , Wu Ji , Cao Lewei , Song Guiqin , Mao Jingxin
Published: April 2024

Rationale:

Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization caused by impaired reabsorption of sodium and chloride ions in the distal renal tubules. We report a case of clinical and genetic characteristics of GS accompanied with Graves disease and adrenocorticotrophic hormone (ACTH)-independent adrenocortical adenoma.

Patient concerns:

The patient is a 45 year old female, was admitted to our hospital, due to a left adrenal gland occupying lesion as the chief complaint.

Diagnosis:

The patient was finally diagnosed as GS with Graves disease and adrenocortical adenoma.

Interventions:

Potassium magnesium aspartate (1788 mg/d, taken orally 3 times a day (supplement a few times a day, intake method, treatment duration). Contains 217.2 mg of potassium and 70.8 mg of magnesium, and potassium chloride (4.5 g/d, taken orally 3 times a day (supplement a few times a day, intake method, and treatment duration); Potassium 2356 mg), spironolactone (20 mg/d, taken orally once a day (supplement a few times a day, intake method, treatment duration). After 3 months of treatment, the patient’s blood potassium fluctuated between 3.3–3.6 mmol/L, and blood magnesium fluctuated between 0.5–0.7 mmol/L, indicating a relief of fatigue symptoms.

Outcomes:

On the day 6 of hospitalization, the symptoms of dizziness, limb fatigue, fatigue and pain were completely relieved on patient. In the follow-up of the following year, no recurrence of the condition was found

Lessons:

The novel c.1444-10(IVS11)G > A variation may be a splicing mutation. The compound heterozygous mutations of the SLC12A3 gene may be the pathogenic cause of this GS pedigree.
The effect of joint position sense therapy on chronic shoulder pain with central sensitization
Authors: Chen Xin , Cha Lisi , Xuan Zhi , Zhang Weiming
Published: April 2024

Background:

Chronic shoulder pain is a common musculoskeletal problem associated with unreleased pain and functional dysfunction that can evolve into central sensitization. Some forms of manual therapy may exacerbate pain and central sensitization. This study investigated the impact of joint position sense therapy (JPST), a moderate joint proprioception training technique, on central sensitization, shoulder functional dysfunction, and pain in patients with chronic shoulder pain compared with more intense exercises or aggressive manual therapies.

Methods:

We assessed the pressure pain threshold (PPT) in 30 patients with and 30 patients without chronic shoulder pain. The assessment focused on 4 muscle sites: deltoid, upper trapezius, brachioradialis, and tibialis anterior. Thirty patients with chronic shoulder pain were randomly divided into the JPST and control groups. The JPST group underwent additional shoulder joint position–sense training. The efficiency outcomes were the disabilities of the arm, shoulder, and hand questionnaire, visual analog scale (VAS), and PPT, evaluated at baseline and after the intervention.

Results:

Significant differences were observed in the PPT values at the brachioradialis (P < .05), deltoid (P < .01), and trapezius (P < .001) among the non-chronic and chronic groups, but not in the tibialis anterior muscle (P > .05). Although both control and JPST interventions effectively improved the disabilities of the arm, shoulder, and hand questionnaire score, pain intensity, and PPT values in the upper limb, the outcomes in the JPST group were significantly different from those in the control group.

Conclusions:

Generalized hyperalgesia changes limited to the upper limbs were observed in patients with chronic shoulder pain. JPST has beneficial effects on pain control and functional dysfunction in patients with chronic shoulder pain.
Evaluating the potential mediating role of ADAMTS13 activity in the relationship between obesity and the severity of COVID-19: A retrospective cohort study
Authors: Hafez Wael , Rashid Asrar , Abuelsaoud Hesham Mohamed , Jose Mohan , Kishk Samy , Gador Muneir , Emoshe Tesfalidet , Abdulaal Fatema , Nair Nivedita , Ahmad Muhammad , Rashid Vanya Jalal , Faheem Youmna , John Steffi , Ahmed Sabah , Daraghmi Ahmed , Soliman Rami , Abdelrahman Ahmed , Mohamed Ahmed Ali , Ghanem Mirvat
Published: April 2024

Obesity and low enzyme A disintegrin and metalloproteinase with thrombospondin type-1 motif-13 (ADAMTS13) activity have been linked to poor coronavirus disease 2019 (COVID-19). Given that obesity may influence ADAMTS13 activity, it is feasible; however, it remains unclear whether ADAMTS13 activity acts as a mediator between obesity and COVID-19 outcomes. We investigated the link between body mass index (BMI) and COVID-19 outcomes, using ADAMTS13 activity as a mediator. ADAMTS13 activity was measured in 86 hospitalized COVID-19 patients. BMI, ADAMTS13 activity, and COVID-19 outcomes were assessed. Obese patients had a high odds ratio for low ADAMTS13 levels. When different levels of ADAMTS13 activity were considered, the severity of COVID-19 in obese patients was 4.5 times that in the normal BMI group. Furthermore, increased coagulopathy indicators correlated with low ADAMTS13 activity. Patients with elevated ALT and AST levels showed a 3 to 4-fold increase in the chances of low ADAMTS13 activity (OR:3.19, 95% CI:1.22–8.90, P = .021; OR:2.17, 95% CI:0.91–5.27, P = .082, respectively). When ADAMTS13 activity was considered, obese patients had greater COVID-19 severity and slower viral clearance than those with normal BMI. Low ADAMTS13 activity and impaired liver function are associated with poor COVID-19 outcomes. These findings encourage researchers to use molecular component identification to study the effects of obesity on the von Willebrand factor (VWF)/ADAMTS13 axis, COVID-19 pathogenesis, and outcomes.
“Internet Plus” continuous nursing for patients with advanced bladder cancer: A retrospective observational study
Authors: Zhang Meiyu , Guo Shuzhen , Gan Sujin , Xu Qiaoli
Published: April 2024

The “Internet Plus” system has made continuous nursing intervention much more feasible to implement, especially in terms of malignant tumors. We aimed to evaluate continuous nursing based on “Internet Plus” for patients diagnosed with bladder cancer with hematuria being treated by drug-eluting bead embolization. This retrospective study included 43 patients, diagnosed with bladder cancer with hemorrhages, who had undergone transcatheter bladder arterial chemoembolization by drug-eluting bead embolization at our hospital between January 2017 and January 2023. They were divided into a control (21 patients) and an observation group (22 patients). The Medical Coping Style Scale, disease knowledge (including regular follow-up and interventional treatment), patient satisfaction, and caregiver burden in both groups were compared on the day of discharge and at the 1-month follow-up for each patient. The confrontation score of the observation group was higher than that of the control group, whereas the resignation and avoidance scores were lower. The disease knowledge was higher in the observation group, and the caregiver burden scores of the observation group were significantly lower. The patient satisfaction scores of the control group (84.7 ± 2.6) were lower than those of the observation group (90.5 ± 5.4). Continuous nursing based on “Internet Plus” could improve the quality of life of patients and their satisfaction regarding the meeting of their and their families’ psychological and nursing needs.
Towards personalized management of early esophageal adenocarcinoma
Authors: Bos Vincent , Chan Man Wai , Pouw Roos E.
Published: April 2024

Purpose of review

This review aims to discuss recent advancements in the endoscopic management of early esophageal adenocarcinoma (T1 EAC).

Recent findings

Patients with high-risk EAC (defined by the presence of deep submucosal invasion, and/or lymphovascular invasion, and/or poor differentiation) have a higher risk of lymph node metastases than those with low-risk EAC. However, more recent, endoscopically-focused studies report a lower risk of lymph node metastases and distant metastases for high-risk EAC than previously assumed. Instead of referring all high-risk EAC patients for esophagectomy after a radical endoscopic resection, an alternative approach involving regular upper endoscopy with endoscopic ultrasound may allow for detection of intra-luminal recurrence and lymph node metastases at an early and potentially curable stage.

Endoscopic resection of mucosal and submucosal EAC might prove to be safe and curative for selected cases in the future, when followed by a strict follow-up protocol. Despite the promising results of preliminary studies, there is an ongoing need for personalized strategies and new risk stratification methods to decide on the best management for individual patients with high-risk T1 EAC.
Demographic and clinical profile of patients undergoing colonoscopy at a tertiary care center in Nepal: a retrospective cross-sectional study
Authors: Sharma Pasanda , Sapkota Prakash , Gurung Ram B. , Silwal Prabhat , Yadav Binay , Gupta Nishchal , Pathak Shikha , Joshi Sahasra , Singh Yadvinder
Published: April 2024

Background:

Colonoscopy is widely used as a tool for diagnosis, screening and treatment of various pathologies in the rectum, colon, and terminal ileum. The aim of this study is to evaluate the demographic, clinical, and histological parameters of the records of patients undergoing colonoscopy at a tertiary care hospital in Nepal.

Materials and methods:

This retrospective cross-sectional study included the hospital records of all patients who underwent colonoscopy from 2015 to 2019 in a tertiary care centre in Nepal.

Results:

A total of 1255 records were included in the study. The mean and standard deviation of age were 43.8 and 19 years, respectively. Among the total study population, 61.9% were males and 38.1% were females. Common indications for colonoscopy included lower gastrointestinal bleeding (27.7%), altered bowel habit (26.9%) and persistent or recurrent abdominal pain (17.3%). Only 3% of the patients who underwent colonoscopy had inadequate bowel preparation. The overall diagnostic yield of colonoscopy was 57.5%. Findings during colonoscopy included colorectal polyp (19.4%), internal haemorrhoids (8.2%) and colitis (6.5%). Having an age of 50 or more years was significantly associated with the presence of colorectal adenocarcinoma (P=0.017, χ2 test) with an odds ratio of 2.35 (95% CI: 1.14, 4.89). Furthermore, having a female sex was found to be significantly associated with the presence of colorectal adenocarcinoma (P=0.012, χ2 test) with an odds ratio of 2.43 (95% CI: 1.19, 4.97).

Conclusion:

In the authors’ study, a smaller proportion of the colonoscopies was aimed at screening for colorectal carcinoma (CRC), when compared to studies in developed countries. The sex predisposition of CRC in the authors’ study is in contrast to the global trend. The authors recommend conducting studies to determine the risk factors and need for CRC screening in the Nepalese population.
Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV
Authors: Moar Preeti , Linn Kyaw , Premeaux Thomas A. , Bowler Scott , Sardarni Urvinder Kaur , Gopalan Bindu Parachalil , Shwe Ei E. , San Thidar , Han Haymar , Clements Danielle , Hlaing Chaw S. , Kyu Ei H. , Thair Cho , Mar Yi Y. , Nway Nway , Mannarino Julie , Bolzenius Jacob , Mar Soe , Aye Aye Mya M. , Tandon Ravi , Paul Robert , Ndhlovu Lishomwa C.
Published: April 2024

Objective:

Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored.

Design:

A cross-sectional study of two independent age-matched cohorts from India [AWH on ART (n = 15), ART-naive (n = 15), and adolescents without HIV (AWOH; n = 10)] and Myanmar [AWH on ART (n = 54) and AWOH (n = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests.

Methods:

Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann–Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers.

Results:

Gal-9 levels were elevated in ART-treated AWH compared with AWOH in both cohorts (all P < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8+ T cells (all P < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains [verbal learning, visuospatial learning, memory, motor skills (all P < 0.05)]. ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents [mean area under the curve (AUC) = 0.837].

Conclusion:

Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.
Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine
Authors: Price Adam D. , Chae Ryan C. , Wallen Taylor E. , Becker Ellen R. , Baucom Matthew R. , Schuster Rebecca M. , England Lisa , Pritts Timothy A. , Goodman Michael D.
Published: April 2024

BACKGROUND

Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor.

METHODS

Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow.

RESULTS

Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model.

CONCLUSION

Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.
Integrated multiomic analysis identifiesTRIP13as a mediator of alveolar epithelial type II cell dysfunction in idiopathic pulmonary fibrosis
Authors: St. Pierre Laurence , Berhan Asres , Sung Eun K. , Alvarez Juan R. , Wang Hongjun , Ji Yanbin , Liu Yixin , Yu Haoze , Meier Angela , Afshar Kamyar , Golts Eugene M. , Lin Grace Y. , Castaldi Alessandra , Calvert Ben A. , Ryan Amy , Zhou Beiyun , Offringa Ite A. , Marconett Crystal N. , Borok Zea
Published: April 2024

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive lung disease urgently needing new therapies. Current treatments only delay disease progression, leaving lung transplant as the sole remaining option. Recent studies support a model whereby IPF arises because alveolar epithelial type II (AT2) cells, which normally mediate distal lung regeneration, acquire airway and/or mesenchymal characteristics, preventing proper repair. Mechanisms driving this abnormal differentiation remain unclear. We performed integrated transcriptomic and epigenomic analysis of purified AT2 cells which revealed genome-wide alterations in IPF lungs. The most prominent epigenetic alteration was activation of an enhancer in thyroid receptor interactor 13 (TRIP13), coinciding withTRIP13upregulation.TRIP13is broadly implicated in epithelial-mesenchymal plasticity and transforming growth factor-β signaling. In cultured human AT2 cells and lung slices, small molecule TRIP inhibitor DCZ0415 prevented acquisition of the mesenchymal gene signature characteristic of IPF, suggesting TRIP13 inhibition as a potential therapeutic approach to fibrotic disease.
Alternating Access of a Neurotransmitter:Sodium Symporter Bacterial Homolog Determined from AlphaFold2 Ensembles and DEER Spectroscopy
Authors: Schwartz Alexandra C. , Stein Richard A. , Gil-Iturbe Eva , Quick Matthias , Mchaourab Hassane S.
Published: April 2024

Neurotransmitter:sodium symporters (NSSs) play critical roles in neural signaling by regulating neurotransmitter uptake into cells powered by sodium electrochemical gradients. Bacterial NSSs orthologs, including MhsT fromBacillus halodurans, have emerged as model systems to understands the structural motifs of alternating access in NSSs and the extent of conservation of these motifs across the family. Here, we apply a novel computational/experimental methodology to illuminate the energy landscape of MhsT alternating access. Capitalizing on our recently developed method, Sampling Protein Ensembles and Conformational Heterogeneity with AlphaFold2 (SPEACH_AF), we derived clusters of MhsT models spanning the transition from inward-facing to outward-facing conformations. Systematic application of double electron-electron resonance (DEER) spectroscopy revealed ligand-dependent movement of multiple structural motifs that underpins MhsT’s conformational cycle. Remarkably, comparative DEER analysis in detergent micelles and lipid nanodiscs highlight the profound effect of the environment on the energetics of conformational changes. Through experimentally-derived selection of collective variables, we present a model of ion and substrate powered transport by MhsT consistent with the conformational cycle derived from DEER. Our findings not only advance the understanding of MhsT’s function but also uncover motifs of conformational dynamics conserved within the broader context of the NSS family and within the LeuT-fold class of transporters. Importantly, our methodological blueprint introduces a novel approach that can be applied across a diverse spectrum of transporters to describe their energy landscapes.

Significance Statement

The neurotransmitter:sodium symporter (NSS) family plays a crucial role in neurotransmitter reuptake, a sodium-dependent process that transports neurotransmitters from the synapse back into the neuron. This study investigates the bacterial tryptophan transporter MhsT, a homolog of human NSSs, using the deep learning method AlphaFold2 in conjunction with double electron-electron resonance spectroscopy. This combined approach enables us to map the energy landscape that dictates the conformational shifts crucial for MhsT’s function. Furthermore, we reveal how the environment modulates the transporter’s dynamics. From our research, we develop a model of MhsT transport that highlights the extent of mechanistic conservation across the NSS family. Additionally, we introduce a comprehensive framework for exploring the energetic landscapes of transporters, effectively integrating computational and experimental methods.
Metabolomics and13C Labelled Glucose Tracing to Identify Carbon Incorporation into Aberrant Cell Membrane Glycans in Cancer
Authors: Reyes-Oliveras Alfredo , Ellis Abigail E. , Sheldon Ryan D. , Haab Brian
Published: April 2024

Cell membrane glycans contribute to immune recognition, signaling, and cellular adhesion and migration, and altered membrane glycosylation is a feature of cancer cells that contributes to cancer progression. The uptake and metabolism of glucose and other nutrients essential for glycan synthesis could underlie altered membrane glycosylation, but the relationship between shifts in nutrient metabolism and the effects on glycans have not been directly examined. To address this possibility, we created a novel method that combines stable isotope tracing with metabolomics to enable direct observations of glucose allocation to nucleotide sugars and cell-membrane glycans. We compared the glucose allocation to membrane glycans of two pancreatic cancer cell lines that are genetically identical but have differing energy requirements. The 8988-S cells had higher glucose allocation to membrane glycans and intracellular pathways relating to glycan synthesis, but the 8988-T cells had higher glucose uptake and commitment of glucose to non-glycosylation pathways. The cells lines differed in requirements of glucose for energy production, resulting in differences in glucose bioavailability for glycan synthesis. The workflow demonstrated here enables studies on the effects of metabolic shifts on the commitment of media nutrients to cell-membrane glycans. The results support a flux-based regulation of glucose commitment glycosylation and a mode of metabolic control of cell functions such signaling, immune recognition, and adhesion and migration.
A microbial derived bile acid acts as GPBAR1 agonist and RORγt inverse agonist and reverses inflammation in inflammatory bowel disease
Authors: Biagioli Michele , Di Giorgio Cristina , Massa Carmen , Marchianò Silvia , Bellini Rachele , Bordoni Martina , Urbani Ginevra , Roselli Rosalinda , Lachi Ginevra , Morretta Elva , Dal Piaz Fabrizio , Charlier Bruno , Fiorillo Bianca , Catalanotti Bruno , Cari Luigi , Nocentini Giuseppe , Ricci Patrizia , Distrutti Eleonora , Sepe Valentina , Zampella Angela , Monti Maria Chiara , Fiorucci Stefano
Published: April 2024

The interplay between the dysbiotic microbiota and bile acids is a critical determinant for development of a dysregulated immune system in inflammatory bowel disease (IBD). Here we have investigated the fecal bile acid metabolome, gut microbiota composition, and immune responses in IBD patients and murine models of colitis and found that IBD associates with an elevated excretion of primary bile acids while secondary, allo- and oxo- bile acids were reduced in both human and mice models of IBD. These changes correlated with the disease severity, mucosal expression of pro-inflammatory cytokines and chemokines, and reduced inflow of anti-inflammatory macrophages and Treg in the gut. Analysis of bile acids metabolome in the feces allowed the identification of five bile acids: 3-oxo-DCA, 3-oxo-LCA, allo-LCA, iso-allo-LCA and 3-oxo-UDCA, whose excretion was selectively decreased in IBD patients and diseased mice. By transactivation assay and docking calculations all five bile acids were shown to act as GPBAR1 agonists and RORγt inverse agonists, skewing Th17/Treg ratio and macrophage polarization toward an M2 phenotype. In a murine model of colitis, administration of 3-oxo-DCA suffices to reverse colitis development and intestinal dysbiosis in a GPBAR1-dependent manner.In vivoadministration of 3-oxo-DCA to colitic mice also reserves disease severity and RORγt activation induced by a RORγt agonist and IL-23, a Th17 inducing cytokine. These results demonstrated intestinal excretion of 3-oxoDCA, a dual GPBAR1 agonist and RORγt inverse agonist, is reduced in IBD and models of colitis and its restitution protects against colitis development, highlighting a potential role for this agent in IBD management.
Changes in wing morphology rather than wingbeat kinematics enabled evolutionary miniaturization of hoverflies
Authors: Le Roy Camille , Tervelde Nina , Engels Thomas , Muijres Florian T.
Published: April 2024

Due to physical scaling laws, size greatly affects animal locomotor ability and performance. Whether morphological and kinematic traits always jointly respond to size variation is however poorly known. Here, we examine the relative importance of morphological and kinematic changes in mitigating the consequence of size on aerodynamic force production for weight support in flying insects, focusing on hovering flight of hoverflies (Syrphidae). We compared the flight biomechanics, aerodynamics, and morphology of eight hoverfly species varying from 5 to 100 mg. Our study reveals no effect of body size on wingbeat kinematics among species, suggesting that morphological rather than kinematic changes may compensate for the reduction in weight support associated with an isometric reduction in size. Computational fluid dynamics simulations confirmed that variations in wing morphology, and not kinematics, allow species of different sizes to generate weight support. We specifically show that relatively larger wings and aerodynamically more effective wing shape have evolved in smaller hoverflies, mitigating the reduction in aerodynamic weight support with decreasing size. Altogether, these results suggest that hovering flight of hoverflies underpins highly specialised wingbeat kinematics, which have been conserved throughout evolution; instead, wing morphological adaptations have enabled the evolutionary miniaturisation of hoverflies.
Molecular dynamics study of stiffness and rupture of axonal membranes
Authors: Majdolhosseini Maryam , Kleiven Svein , Villa Alessandra
Published: April 2024

Diffuse axonal injury (DAI), characterized by widespread damage to axons throughout the brain, represents one of the most devastating and difficult-to-treat forms of traumatic brain injury. Different theories exist about the mechanism of DAI, among which one hypothesis states that membrane poration of the axons initiates DAI. To investigate the hypothesis, molecular models of axonal membranes, incorporating 25 different lipids distributed asymmetrically in the leaflets, were developed using a coarse-grain description and simulated using molecular dynamics techniques. Different protein concentrations were embedded inside the lipid bilayer to describe the different sub-cellular parts in myelinated and unmyelinated axons. The models were investigated in equilibration and under deformation to characterize the structural and mechanical properties of the membranes, and comparisons were made with other subcellular parts, particularly myelin. Employing a bottom-top approach, the results were coupled with a finite element model representing the axon at the cell level. The results indicate that pore formation in the node-of-Ranvier occurs at a lower rupture strain compared to other axolemma parts, whereas myelin poration exhibits the highest rupture strains among the investigated models. The observed rupture strain for the node-of-Ranvier aligns with experimental studies, indicating a threshold for injury at axonal strains exceeding 10 − 13%epending on the strain rate. The results indicate that the hypothesis suggesting mechanoporation triggers axonal injury cannot be dismissed, as this phenomenon occurs within the threshold of axonal injury.

Highlights

Developing a realistic molecular model of axolemma based on experimental data about its lipid composition

Investigating how lipid composition and protein concentration affect the membrane’s structural and mechanical properties

Identifying the most vulnerable regions of the axonal membrane
Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma
Authors: Ghoshal Delta , Petersen Ingrid , Ringquist Rachel , Kramer Liana , Bhatia Eshant , Hu Thomas , Richard Ariane , Park Reda , Corbin Jenna , Agarwal Savi , Thomas Abel , Ramirez Sebastian , Tharayil Jacob , Downey Emma , Ketchum Frank , Ochal Abigail , Sonthi Neha , Lonial Sagar , Kochenderfer James N. , Tran Reginald , Zhu Mandy , Lam Wilbur A. , Coskun Ahmet F. , Roy Krishnendu
Published: April 2024

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within ourin vitrosystem and successfully flowed in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics.

TEASER

A multiple myeloma model can study why the disease is still challenging to treat despite options that work well in other cancers.