bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between sexual behaviour and head and neck cancer in the French West Indies: a case-control study based on an Afro-Caribbean population
Authors: Auguste Aviane , Gaete Stanie , Michineau Léah , Herrmann-Storck Cécile , Joachim Clarisse , Duflo Suzy , Deloumeaux Jacqueline , Luce Danièle
Published: May 2023

Background

Worldwide, a significant proportion of head and neck cancers is attributed to the Human papillomavirus (HPV). It is imperative that we acquire a solid understanding of the natural history of this virus in head and neck squamous cell carcinoma (HNSCC) development. Our objective was to investigate the role of sexual behaviour in the occurrence of HNSCC in the French West Indies. Additionally, we evaluated the association of high risk of HPV (Hr-HPV) with sexual behaviour in risk of cancer.

Methods

We conducted a population-based case-control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds-ratios (OR), and their 95% confidence intervals (CI).

Results

Compared to persons who never practiced oral sex, those who practiced at least occasionally had a lower HNSCC risk. First sexual intercourse after the age of 18 year was associated with a 50% reduction of HNSCC risk, compared to those who began before 15 years. HNSCC risk was significantly reduced by 60% among persons who used condoms at least occasionally. The associations for ever condom use and oral sex were accentuated following the adjustment for high-risk HPV (Hr-HPV). Oral Hr-HPV was associated with several sexual behaviour variables among HNSCC cases. However, none of these variables were significantly associated with oral HPV infections in the population controls.

Conclusion

First intercourse after 18 years, short time interval since last intercourse and ever condom use were inversely associated with HNSCC independently of oral Hr-HPV infection. Sources of transmission other than sexual contact and the interaction between HPV and HIV could also play a role in HNSCC etiology.
Variability in mental health reporting among refugees and migrants in need of protection: new evidence from a weekly panel survey
Authors: Weitzman Abigail , Blanton Matthew , Camacho Gilbert Brenes
Published: May 2023

Background

The global population of refugees and other migrants in need of protection (MNP) is swiftly growing. Prior scholarship highlights that MNP have poorer mental health than other migrant and non-migrant populations. However, most scholarship on MNP mental health is cross-sectional, leaving open questions about temporal variability in their mental health.

Methods

Leveraging novel weekly survey data from Latin American MNP in Costa Rica, we describe the prevalence, magnitude, and frequency of variability in eight indicators of self-reported mental health over 13-weeks; highlight which demographic characteristics, incorporation hardships, and violence exposures are most predictive of variability; and determine how variability corresponds to baseline mental health.

Results

For all indicators, most respondents (> 80%) varied at least occasionally. Typically, respondents varied 31% to 44% of weeks; for all but one indicator they varied widely—by ~ 2 of 4 possible points. Age, education, and baseline perceived discrimination were most consistently predictive of variability. Hunger and homelessness in Costa Rica and violence exposures in origin also predicted variability of select indicators. Better baseline mental health was associated with less subsequent variability.

Conclusions

Our findings highlight temporal variability in repeated self-reports of mental health among Latin American MNP and further highlight sociodemographic heterogeneity therein.
Mechanical study of the application of compression screw nails in the cross-inverted triangular pattern for internal fixation of femoral neck fractures
Authors: Wang Min , Wang Yunlong , Zou Fa , Tan Lin , Wang Yunjuan
Published: May 2023

Objective

To design a cross-inverted triangular pattern to insert compression screw nails for the treatment of femoral neck fractures and to compare the biomechanics of inserting compression screw nails in cross-inverted triangular patterns and inverted triangular patterns.

Methods

The reasonableness of the model is first analyzed using finite elements. A total of 6 adult human specimens were selected, of which 3 males and 3 females were divided into the A1, B1, and C1 groups and the A2, B2, and C2 groups by the random number table method. The A1 and A2 groups were made into subhead femoral neck fracture models, the B1 and B2 groups were made into trans-neck femoral neck fracture models, and the C1 and C2 groups were made into basal femoral neck fracture models. The right femur of each group had a compression screw nail inserted in the crossed-inverted triangular pattern, and the left femur of each group had a compression screw nail inserted in the inverted triangular pattern. The static compression test was performed by an electronic universal testing machine. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were read according to the pressure-displacement curve drawn in the experiment.

Results

The finite element analysis showed that the cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were greater than those of the right femur in the A1, A2, B1, B2 and C2 groups, while the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were smaller than those of the right femur in the C1 group. There was no statistically significant difference in the maximum load of the femoral neck or the load of 3.00 mm axial displacement of the femoral head between the A1 and A2 groups, the B1 and B2 groups, or the C1 and C2 groups (P > 0.05). After the K-S test, the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were normally distributed (P = 0.20), and the LSD-t test was conducted for the two load data; the difference was not statistically significant (P = 0.235).

Conclusion

The effect of compression screw nails in the cross-inverted triangular pattern was the same in males and females, and stability was better in the fixation of subhead and trans-neck femoral neck fractures. However, its stability in fixation of basal femoral neck fracture is worse than that of the inverted triangular pattern. The cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail.
Factors affecting the scientific research ability and the corresponding countermeasures in clinical postgraduates
Authors: Fu De-Qiang , Huang Yin-Qiong , Que Yu-Hui , Hong Yu , Lin Jian-Qing
Published: May 2023

Background

Scientific research ability (SRA) is very important for clinical postgraduates. However, the factors affecting students' SRA are constantly changing with the development of medicine. The aim of this study was to investigate the current situation of SRA in clinical postgraduates and exploring the potential factors and the corresponding countermeasures under the background of new medical science.

Methods

A total of 133 postgraduates (first- or second-year) were investigated by questionnaire in the Second Affiliated Hospital of Fujian Medical University. All results were analyzed by R software.

Results

In terms of the SRA, academic-degree postgraduate students (ADPSs) were significantly better than professional-degree postgraduate students (PDPSs) (P = 0.001), the students with scientific research interest were remarkably better than those without scientific research interest (P = 0.004), the students who mastered statistical analysis methods were more prominent than those who did not (P = 0.007), the students with paper-writing skills were obviously superior to those without it (P = 0.003), and the second-year students were notably better than the first-year students (P = 0.003). Stratified analysis by the above factors except the degree type showed no significant difference in the first-year postgraduates. In the second-year postgraduates, the ADPSs were remarkably superior to the PDPSs (P = 0.002), the students with scientific research interest were obviously better than those without scientific research interest (P = 0.014), the students with more time investment in scientific research were more prominent than those with less time investment in scientific research (P = 0.025), the students with paper-writing skills were notably superior to those without it (P = 0.031), and the students with plotting ability were better than those without it (P = 0.013).

Conclusion

The important factors affecting the SRA of clinical postgraduates include the degree type, the grade of student, scientific research interest, time investment in scientific research, statistical analysis methods, paper-writing skills, plotting ability. In short, earlier systematic SRA training contributes to the improvement of SRA in clinical postgraduates, especially in PDPSs.
Experiences with telemedicine among family medicine residents at king saud university medical city during the COVID-19 pandemic: a cross-sectional study
Authors: AlFawaz Ibrahim , Alrasheed Abdullah A.
Published: May 2023

Background

The healthcare system experienced various challenges during the coronavirus disease 2019 (COVID-19) pandemic, and a wide range of safety measures were implemented, including limiting the number of patients allowed to visit primary care clinics and follow-up through telemedicine clinics. These changes have accelerated the growth of telemedicine in medical education and affected the training of family medicine residents throughout Saudi Arabia. Therefore, this study aimed to evaluate the experiences of family medicine residents with telemedicine clinics as a part of their clinical training during the COVID-19 pandemic.

Methods

A cross-sectional study was conducted with 60 family medicine residents at King Saud University Medical City, Riyadh, Saudi Arabia. An anonymous 20-item survey was administered between March and April 2022.

Results

The participants included 30 junior and 30 senior residents, with a 100% response rate. The results revealed that most (71.7%) participants preferred in-person visits during residency training, and only 10% preferred telemedicine. In addition, 76.7% of the residents accepted the inclusion of telemedicine clinics in training if such clinics constituted not more than 25% of the training program. Moreover, most participants reported receiving less clinical experience, less supervision, and less discussion time with the attending supervisor when training in telemedicine clinics compared with in-person visits. However, most (68.3%) participants gained communication skills through telemedicine.

Conclusions

Implementing telemedicine in residency training can create various challenges in education and influence clinical training through less experience and less clinical interaction with patients if it is not structured well. With the growth of digital healthcare, further structuring and testing of a paradigm that involves using telemedicine in residents’ training programs prior to implementation should be considered for better training and patient care.
Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study
Authors: Li Jin , Qin Shukui , Wen Lu , Wang Junsheng , Deng Wenying , Guo Weijian , Jia Tongfu , Jiang Da , Zhang Guifang , He Yifu , Ba Yi , Zhong Haijun , Wang Lin , Lin Xiaoyan , Yang Jianwei , Zhao Jun , Bai Yuxian , Wu Xiangyuan , Gao Feng , Sun Guogui , Wu Yongjuan , Ye Feng , Wang Qiong , Xie Zhong , Yi Tienan , Huang Yong , Yu Guohua , Lu Lin , Yuan Ying , Li Wei , Liu Likun , Sun Yuping , Sun Ying , Yin Lifeng , Hou Zhiguo
Published: May 2023

Background

Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings.

Methods

Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method.

Results

Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1).

Conclusions

The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment.

Trial registration

This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.
Exploring the antimicrobial, antiviral, antioxidant, and antitumor potentials of marine Streptomyces tunisiensis W4MT573222 pigment isolated from Abu-Qir sediments, Egypt
Authors: Ibrahim Walaa M. , Olama Zakia A. , Abou-elela G. M. , Ramadan Heba S. , Hegazy Ghada E. , El Badan Dalia El S.
Published: May 2023

Due to the therapeutic importance of microbial pigments, these pigments are receiving the attention of researchers. In this present study 60 isolates were isolated from sediments of Abu-Qir coast of the Mediterranean sea, Alexandria, Egypt, out of which 12 were considered as pigmented actinomycetes. Streptomyces sp. W4 was characterized by small round green pigmented colonies when grown on starch-casein agar medium. The green pigment was extracted using a mixture of acetone-methanol (7:3 v/v). The antimicrobial, antioxidant, antiviral, and anticancer activities of the green pigment produced by Streptomyces sp.W4 were investigated. The pigment was characterized using FTIR, Raman spectroscopy, EDX and GC–MS. The results revealed that the pigment has antibacterial and antifungal activity and also showed inhibition of HAV 78% but its antiviral activity against the Adenovirus was weak. The results proved the safety of the pigment toward normal cells and anticancer activity against three different cancer cell lines HepG-2 (liver cancer cell line), A549 (lung cancer cell line), and PAN1 (pancreas cancer cell line). The pigment was combined with 9 antibiotics and then tested against the Gram-negative bacterium Enterococcus faecalis using disc diffusion bioassay. LEV showed an antagonistic effect, while CXM and CIP showed a synergistic effect.
Predictors of caregiver adherence to administration of amodiaquine during delivery of seasonal malaria chemoprevention in Nigeria, Burkina Faso, Chad, and Togo
Authors: Ibinaiye Taiwo , Oresanya Olusola , Oguoma Chibuzo , Aidenagbon Adaeze , Ogunmola Olabisi , Rassi Christian , Richardson Sol
Published: May 2023

Background

Malaria is the leading cause of morbidity and mortality among infants and children under-five in sub-Saharan Africa. In the Sahel, seasonal malaria chemoprevention (SMC) is delivered door-to-door in monthly cycles. In each cycle, children are administered sulfadoxine–pyrimethamine (SP) plus amodiaquine (AQ) on Day 1 by community distributors, and AQ on Day 2 and Day 3 by caregivers. Non-adherence to AQ administration by caregivers has implications for emergence of antimalarial resistance.

Methods

Predictors of non-adherence to administration of AQ on Day 2 and Day 3 among caregivers of children aged 3–59 months who had received Day 1 SP and AQ during the last 2020 SMC cycle (n = 12,730) were analysed using data from SMC coverage surveys in Nigeria, Burkina Faso and Togo, and fitting multivariate random-effects logistic regression models.

Results

Previous adverse reaction to SMC medicines by eligible children (OR: 0.29, 95% CI 0.24–0.36, p < 0.001), awareness of the importance of administering Day 2 and Day 3 AQ (OR: 2.19, 95% CI 1.69–2.82, p < 0.001), caregiver age, and home visits to caregivers delivered by the Lead Mothers intervention in Nigeria (OR: 2.50, 95% CI 1.93–2.24, p < 0.001), were significantly associated with caregiver adherence to Day 2 and Day 3 AQ administration.

Conclusions

Increasing caregivers’ knowledge of SMC and interventions such as Lead Mothers have the potential to improve full adherence to AQ administration.
Psychometric evaluation of the traditional Chinese version of PedsQL™ 3.0 cardiac module scale in adolescents with congenital heart disease: reliability, validity, measurement invariance, and adolescent-parent agreement
Authors: Huang Yong-Chen , Chen Yueh-Chih , Gau Bih-Shya , Wang Jou-Kou , Chang Shu-Hui , Yang Hsiao-Ling
Published: May 2023

Background

In recent decades, 95% of children with congenital heart disease (CHD) can survive to adolescence and adulthood. However, adolescents with CHD are prone to poorer health-related quality of life (HRQoL). It is imperative to develop a reliable and valid instrument for health professionals to monitor the HRQoL. This study aims to: (1) evaluate the psychometric properties of the traditional Chinese version of Pediatric Quality of Life™ 3.0 Cardiac Module (PedsQL-CM) and measurement invariance across adolescents with CHD and their parents; and (2) investigate the adolescent-parent agreement in HRQoL.

Methods

A total of 162 adolescents and 162 parents were recruited. Internal consistency was examined using Cronbach’s alpha and McDonald’s Omega. The criterion-related validity was evaluated with intercorrelations between the PedsQL-CM and PedsQL™ 4.0 Generic Core (PedsQL-GC) Scale. The construct validity was examined by second-order confirmatory factor analysis (CFA). Measurement invariance was evaluated using the multi-group CFA. The adolescent-parent agreement was analyzed with the intraclass correlation (ICC), paired t-tests, and Bland–Altman plots.

Results

PedsQL-CM showed acceptable internal consistency (self-reports 0.88, proxy-reports 0.91). The intercorrelations were medium to large effect size (self-reports 0.34–0.77, proxy-reports 0.46–0.68). The CFA supported the construct validity (CFI = 0.967, TLI = 0.963, RMSEA = 0.036, 90% CI = 0.026–0.046, SRMR = 0.065). The multi-group CFA proved scalar invariance between self and parent proxy-reports. Parents significantly underestimated their adolescents’ HRQoL in cognitive problems (Cohen’s d = 0.21) and communication (Cohen’s d = 0.23) subscales, while there was a negligible difference in total HRQoL (Cohen’s d = 0.16). ICCs were poor to moderate effect size with the highest and lowest agreement in heart problems and treatment subscale (ICC = 0.70) and communication subscale (ICC = 0.27), respectively. The Bland–Altman plots showed lesser variability in the heart problem and treatment subscale and the total scale.

Conclusion

The traditional Chinese version of PedsQL-CM has acceptable psychometric properties to measure disease-specific HRQoL in adolescents with CHD. Parents may be proxies for adolescents with CHD to rate total HRQoL. When the patient-reported score is the primary outcome, the proxy-reported score could serve as a secondary outcome for research and clinical evaluation.
Bach Mai Procedure for complete mesocolic excision, central vascular ligation, and D3 lymphadenectomy in total laparoscopic right hemicolectomy: a prospective study
Authors: Nguyen Ngoc Hung , Vu Xuan Vinh , Nguyen Vu Quang , Nguyen The Hiep , Du Nguyen Huy , Luong Tuan Hiep , Nguyen Thanh Khiem , Nguyen Ham Hoi
Published: May 2023

Purpose

Total laparoscopic right hemicolectomy with complete mesocolic excision (CME), central vascular ligation (CVL), and D3 lymphadenectomy is still the most challenging colon procedures for gastrointestinal surgeons. We herein report the technical details and our preliminary experience of Bach Mai Procedure — a novel-combining (cranial, medial to lateral, and caudal) approach with early resection of the terminal ileum.

Methods

The dissection stage was central vascular isolation and ligation by a combined multiple approaches in the following four steps: cranial approach, dissecting along the inferior aspect of pancreatic isthmus to reveal the middle colic vessels and the anterior aspect of the superior mesentery vein and then exposed the right gastroepiploic vein and the trunk of Henle; medial-to-lateral approach, exposing the surgical axis — the superior mesenteric vascular axis and then early resection of the terminal ileum to open the dissection from the bottom up; and caudal approach, radical ligation of the ileocecal artery and right colic artery (central vascular ligation), lymph node dissection (D3 lymphadenectomy), and resecting the Toldt fascia of the colon to release the entire right colon from the abdominal wall.

Results

In 12 months, there were 32 cases of primary right-sided colon malignancies that have undergone tLRHD3, CME/CVL based on the Bach Mai Procedure. In 3 cases (9.4%), the tumor site was hepatic flexure. The median of lymph node number (LNN) was 38, with the maximum number which was 101. No serious postoperative complications (grade 3 or higher) neither inhospital mortality was detected.

Conclusion

This Bach Mai procedure, a novel-combining approach with early resection of the terminal ileum, is technically feasible and safe for tLRHD3, CME/CVL. Further investigations and follow-up must be proceeded to evaluate the long-term outcomes of our technique.
Recurrent, life-threatening PE in the setting of popliteal vein aneurysm in pregnancy: a case report
Authors: McBride S. Ainslie , Rannelli Luke A. , Cantle Paul M.
Published: May 2023

Background

Popliteal vein aneurysms (PVA) are a rare clinical entity with unknown etiology that pose a significant risk for venous thromboembolic events (VTE). The current literature supports anticoagulation and operative management. There are few case reports of PVA in pregnancy. We present a unique case of a pregnant patient with recurrent pulmonary embolism (PE) in the setting of PVA with intra-aneurysmal thrombosis who ultimately underwent surgical excision.

Case presentation

A previously healthy 34-year-old G2P1 at 30 weeks gestation presented to the emergency department with shortness of breath and chest pain. She was diagnosed with PE and subsequently required intensive care unit (ICU) admission and thrombolysis for a massive PE. While on a therapeutic dose of tinzaparin she had recurrence of PE in the post-partum period. She was treated with supratherapeutic tinzaparin and subsequently transitioned to warfarin. She was found to have a PVA and ultimately underwent successful PVA ligation. She remains on anticoagulation for secondary prevention of VTE.

Conclusions

PVA are a rare but potentially fatal source of VTE. Patients most commonly present with symptoms of PE. The risk of VTE is elevated in the pro-thrombotic states of pregnancy and the post-partum period due to both physiologic and anatomical changes. The recommended management of PVA with PE is anticoagulation and surgical resection of the aneurysm, however this can be complicated in the setting of pregnancy. We demonstrated that pregnant patients with PVA can be temporized with medical management to avoid surgical intervention during pregnancy, but require close symptom monitoring and serial imaging to reassess the PVA, with high index of suspicion for recurrent VTE. Ultimately, patients with PVA and PE should undergo surgical resection to reduce the risk of recurrence and long-term complications. The ideal duration of post-operative anticoagulation remains unclear, and should likely be decided on based on risks, benefits, values, and shared decision making with the patient and their care provider.
Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/β-catenin/c-Myc/SOX2 pathway in colorectal cancer
Authors: Li Zhengguang , Yang Zhirong , Liu Wei , Zhu Wanglong , Yin Lan , Han Zhenyu , Xian Yu , Wen Jie , Tang Hualong , Lin Xinyue , Yang Yuhan , Wang Jingyi , Zhang Kun
Published: May 2023

Background

Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC).

Methods

UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/β-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo.

Results

DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/β-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/β-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice.

Conclusion

DVL3 promoted EMT and CSLCs properties of CRC via Wnt/β-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.
SYTL2 promotes metastasis of prostate cancer cells by enhancing FSCN1-mediated pseudopodia formation and invasion
Authors: Li Zean , Tao Yiran , Gao Ze , Peng Shirong , Lai Yiming , Li Kaiwen , Chen Xu , Huang Hai
Published: May 2023

Background

Metastatic prostate cancer (mPCa) has a poor prognosis with limited treatment options. The high mobility of tumor cells is the key driving characteristic of metastasis. However, the mechanism is complex and far from clarified in PCa. Therefore, it is essential to explore the mechanism of metastasis and discover an intrinsic biomarker for mPCa.

Methods

Transcriptome sequencing data and clinicopathologic features of PCa from multifarious public databases were used to identify novel metastatic genes in PCa. The PCa tissue cohort containing 102 formalin-fixed paraffin-embedded (FFPE) samples was used to evaluate the clinicopathologic features of synaptotagmin-like 2 (SYTL2) in PCa. The function of SYTL2 was investigated by migration and invasion assays and a 3D migration model in vitro and a popliteal lymph node metastasis model in vivo. We performed coimmunoprecipitation and protein stability assays to clarify the mechanism of SYTL2.

Results

We discovered a pseudopodia regulator, SYTL2, which correlated with a higher Gleason score, worse prognosis and higher risk of metastasis. Functional experiments revealed that SYTL2 promoted migration, invasion and lymph node metastasis by increasing pseudopodia formation in vitro and in vivo. Furthermore, SYTL2 induced pseudopodia formation by enhancing the stability of fascin actin-bundling protein 1 (FSCN1) by binding and inhibiting the proteasome degradation pathway. Targeting FSCN1 enabled rescue and reversal of the oncogenic effect of SYTL2.

Conclusions

Overall, our study established an FSCN1-dependent mechanism by which SYTL2 regulates the mobility of PCa cells. We also found that the SYTL2-FSCN1-pseudopodia axis may serve as a pharmacological and novel target for treating mPCa.
Systematic levels of IL-29 and microRNA185-5p were not associated with severe COVID-19 in the Iranian population
Authors: Sarrafi Omidreza , Kariminik Ashraf , Arababadi Mohammad Kazemi
Published: May 2023

Background

Increased systematic pro-inflammatory cytokines is the main cause of the inflammatory conditions of the hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this project, serum levels of IL-29 and whole blood levels of microRNA-185-5p (miR-185-5p) were evaluated in the hospitalized SARS-CoV-2 infected patients.

Methods

This project was performed on the 60 hospitalized SARS-CoV-2 infected patients and 60 healthy controls to evaluate IL-29 and miR185-5p expression levels. IL-29 expression was explored using enzyme linked immunoassay (ELISA), while miR185-5p was evaluated using Real-Time PCR techniques.

Results

The results demonstrated that neither IL-29 serum levels nor relative expressions of miR-185-5p were significantly different between patients and healthy controls.

Conclusion

Due to the results that are presented here, systematic levels of IL-29 and miR-185-5p cannot be considered as the main risk factors for induction of inflammation in the hospitalized SARS-CoV-2 infected patients.
Switch from a ritonavir to a cobicistat containing antiretroviral regimen and impact on tacrolimus levels in a kidney transplant recipient
Authors: Erba Andrea , Marzolini Catia , Rentsch Katharina , Stoeckle Marcel , Battegay Manuel , Mayr Michael , Weisser Maja
Published: May 2023

Background

Solid-organ transplantation due to end-stage organ disease is increasingly performed in people living with HIV. Despite improved transplant outcomes, management of these patients remains challenging due to higher risk for allograft rejection, infection and drug–drug interactions (DDIs). Complex regimens for multi-drug resistant HIV-viruses may cause DDIs particularly if the regimen contains drugs such as ritonavir or cobicistat.

Case presentation

Here we report on a case of an HIV-infected renal transplant recipient on long-term immunosuppressive therapy with mycophenolate mofetil and tacrolimus dosed at 0.5 mg every 11 days due to the co-administration of a darunavir/ritonavir containing antiretroviral regimen. In the presented case the pharmacokinetic booster was switched from ritonavir to cobicistat for treatment simplification. A close monitoring of tacrolimus drug levels was performed in order to prevent possible sub- or supratherapeutic tacrolimus trough levels. A progressive decrease in tacrolimus concentrations was observed after switch requiring shortening of tacrolimus dosing interval. This observation was unexpected considering that cobicistat is devoid of inducing properties.

Conclusions

This case highlights the fact that the pharmacokinetic boosters ritonavir and cobicistat are not fully interchangeable. Therapeutic drug monitoring of tacrolimus is warranted to maintain levels within the therapeutic range.
SciComm Optimizer for Policy Engagement: a randomized controlled trial of the SCOPE model on state legislators’ research use in public discourse
Authors: Scott J. Taylor , Collier K. Megan , Pugel Jessica , O’Neill Patrick , Long Elizabeth C. , Fernandes Mary A. , Cruz Katherine , Gay Brittany , Giray Cagla , Crowley D. Max
Published: May 2023

Background

While prior work has revealed conditions that foster policymakers’ use of research evidence, few studies have rigorously investigated the effectiveness of theory-based practices. Specifically, policymakers are most apt to use research evidence when it is timely, relevant, brief, and messaged appropriately, as well as when it facilitates interactive engagement. This study sought to experimentally evaluate an enhanced research dissemination intervention, known as the SciComm Optimizer for Policy Engagement (SCOPE), implemented during the COVID-19 pandemic among US state legislators.

Methods

State legislators assigned to health committees and their staff were randomized to receive the SCOPE intervention. This involved providing academic researchers with a pathway for translating and disseminating research relevant to current legislative priorities via fact sheets emailed directly to officials. The intervention occurred April 2020–March 2021. Research language was measured in state legislators’ social media posts.

Results

Legislators randomized to receive the intervention, relative to the control group, produced 24% more social media posts containing research language related to COVID-19. Secondary analyses revealed that these findings were driven by two different types of research language. Intervention officials produced 67% more COVID-related social media posts referencing technical language (e.g., statistical methods), as well as 28% more posts that referenced research-based concepts. However, they produced 31% fewer posts that referenced creating or disseminating new knowledge.

Conclusions

This study suggests that strategic, targeted science communication efforts may have the potential to change state legislators’ public discourse and use of evidence. Strategic science communication efforts are particularly needed in light of the role government officials have played in communicating about the pandemic to the general public.
The relationship between gut microbiota and susceptibility to type 2 diabetes mellitus in rats
Authors: An Yongcheng , Dai Hongyu , Duan Yuhui , Cheng Long , Shi Lu , He Changhao , Wang Chen , Lv Yinglan , Li Huimin , Zhang Huilin , Huang Yan , Fu Wanxin , Sun Weiguang , Zhao Baosheng
Published: May 2023

Purpose

The purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.

Methods

Thirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.

Results

G__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.

Conclusions

G__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.
A systematic overview of rare disease patient registries: challenges in design, quality management, and maintenance
Authors: Hageman Isabel C. , van Rooij Iris A.L.M. , de Blaauw Ivo , Trajanovska Misel , King Sebastian K.
Published: May 2023

Patient registries serve to overcome the research limitations inherent in the study of rare diseases, where patient numbers are typically small. Despite the value of real-world data collected through registries, adequate design and maintenance are integral to data quality. We aimed to describe an overview of the challenges in design, quality management, and maintenance of rare disease registries.

A systematic search of English articles was conducted in PubMed, Ovid Medline/Embase, and Cochrane Library. Search terms included “rare diseases, patient registries, common data elements, quality, hospital information systems, and datasets”. Inclusion criteria were any manuscript type focused upon rare disease patient registries describing design, quality monitoring or maintenance. Biobanks and drug surveillances were excluded.

A total of 37 articles, published between 2001 and 2021, met the inclusion criteria. Patient registries covered a wide range of disease areas and covered multiple geographical locations, with a predisposition for Europe. Most articles were methodological reports and described the design and setup of a registry. Most registries recruited clinical patients (92%) with informed consent (81%) and protected the collected data (76%). Whilst the majority (57%) collected patient-reported outcome measures, only few (38%) consulted PAGs during the registry design process. Few reports described details regarding quality management (51%) and maintenance (46%).

Rare disease patient registries are valuable for research and evaluation of clinical care, and an increasing number have emerged. However, registries need to be continuously evaluated for data quality and long-term sustainability to remain relevant for future use.
Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial
Authors: Wieruszewski Patrick M. , Bellomo Rinaldo , Busse Laurence W. , Ham Kealy R. , Zarbock Alexander , Khanna Ashish K. , Deane Adam M. , Ostermann Marlies , Wunderink Richard G. , Boldt David W. , Kroll Stew , Greenfeld Chuck R. , Hodges Tony , Chow Jonathan H. ,   the Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators
Published: May 2023

Background

High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II).

Methods

Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55–70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation.

Results

Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274–0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644–1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups.

Conclusions

This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial.

Trial registration: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.
Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa—a multiphase optimization strategy (MOST) approach using a fractional factorial design
Authors: Jennings Lauren , West Rebecca L. , Halim Nafisa , Kaiser Jeanette L. , Gwadz Marya , MacLeod William B. , Gifford Allen L. , Haberer Jessica E. , Orrell Catherine , Sabin Lora L.
Published: May 2023

Background

South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town.

Methods

We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial.We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package.

Discussion

To our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic.

Trial registration

ClinicalTrials.gov NCT05040841. Registered on 10 September 2021.
Investigation of the relationship between sleep-related parameters and metabolic syndrome (MetS) among youths in the Southeast of Iran
Authors: Kazemi Majid , Khalili Parvin , Kazemi Mahsa , Hasani Hadi , Sadeghi Marjan , Jamali Zahra
Published: May 2023

Background and aim

There are few studies and inconsistent findings on the role of sleep-related parameters in the development of metabolic syndrome (MetS) among youths. In this study, we aim to investigate the relationship between sleep-related parameters and MetS among youths in a large sample size in Rafsanjan, a region in the southeast of Iran.

Methods

The current cross-sectional study was performed on 3,006 young adults aged 15–35, who registered for Rafsanjan Youth Cohort Study (RYCS), as part of Rafsanjan Cohort Study (RCS)). In fact, RCS is a branch of the prospective epidemiological research studies in Iran (PERSIAN). In the present study, we included 2,867 youths after excluding some subjects with missing information on MetS components. MetS was diagnosed based on Adult Treatment Panel III (ATP III) criteria. Besides, data on sleep-related parameters were collected by self-report questionnaires.

Results

The overall prevalence of MetS was 7.74% among the participants. In addition, bedtime, wake time, napping, night shift work, and sleep duration per night and day had no association with the higher odds of having MetS. In contrast, long sleep duration at night was associated with the lower odds of high waist circumference (WC) (OR: 0.82,95% CI :0.67–0.99).

Conclusion

In the present study, long sleep duration at night was associated with lower odds of central obesity. However, more longitudinal studies with the objective measurement of sleep-related parameters are needed to verify the associations reported in the current study.
Acute encephalomyelitis in a 52-year-old male post messenger ribonucleic acid severe acute respiratory syndrome coronavirus 2 vaccination: a case report
Authors: Alebna Pamela Lamisi , Shahid Muhammad Ahmad , Brannan Timothy , Shen Ting , Marian Valentin
Published: May 2023

Background

Acute disseminated encephalomyelitis is a well-known, but rare, side effect of some vaccines, or symptom following a febrile illness.

Case

A 69-year-old, otherwise healthy Hispanic male presented with acute fever, confusion, and later progressive weakness after receiving the first dose of the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 vaccine. Considering the progressive deterioration of the patient, despite being on multiple immunosuppressive agents, a brain biopsy was obtained, which revealed nonspecific meningoencephalitis.

Conclusion

In this case, we highlight the need for a regulatory framework to assist clinicians and patients with coverage of treatment for acute disseminated encephalomyelitis. The use of intravenous immunoglobulin in conjunction with glucocorticoids seems to be an effective treatment option.