bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Catch-UP!: a realist evaluation of an innovative multi-disease screening and vaccination tool in UK primary care for at-risk migrant patients
Authors: Carter Jessica , Goldsmith Lucy P. , Knights Felicity , Deal Anna , Jayakumar Subash , Crawshaw Alison F. , Seedat Farah , Aspray Nathaniel , Zenner Dominik , Harris Philippa , Ciftci Yusuf , Wurie Fatima , Majeed Azeem , Harris Tess , Matthews Philippa , Hall Rebecca , Requena-Mendez Ana , Hargreaves Sally
Published: October 2024

Background

Migrants to the UK face disproportionate risk of infections, non-communicable diseases, and under-immunisation compounded by healthcare access barriers. Current UK migrant screening strategies are unstandardised with poor implementation and low uptake. Health Catch-UP! is a collaboratively produced digital clinical decision support system that applies current guidelines (UKHSA and NICE) to provide primary care professionals with individualised multi-disease screening (7 infectious diseases/blood-borne viruses, 3 chronic parasitic infections, 3 non-communicable disease or risk factors) and catch-up vaccination prompts for migrant patients.

Methods

We carried out a mixed-methods process evaluation of Health Catch-UP! in two urban primary healthcare practices to integrate Health Catch-UP! into the electronic health record system of primary care, using the Medical Research Council framework for complex intervention evaluation. We collected quantitative data (demographics, patients screened, disease detection and catch-up vaccination rates) and qualitative participant interviews to explore acceptability and feasibility.

Results

Ninety-nine migrants were assessed by Health Catch-UP! across two sites (S1, S2). 96.0% (n = 97) had complete demographics coding with Asia 31.3% (n = 31) and Africa 25.2% (n = 25), the most common continents of birth (S1 n = 92 [48.9% female (n = 44); mean age 60.6 years (SD 14.26)]; and S2 n = 7 [85.7% male (n = 6); mean age 39.4 years (SD16.97)]. 61.6% (n = 61) of participants were eligible for screening for at least one condition and uptake of screening was high 86.9% (n = 53). Twelve new conditions were identified (12.1% of study population) including hepatitis C (n = 1), hypercholesteraemia (n = 6), pre-diabetes (n = 4), and diabetes (n = 1). Health Catch-UP! identified that 100% (n = 99) of patients had no immunisations recorded; however, subsequent catch-up vaccination uptake was poor (2.0%, n = 1). Qualitative data supported acceptability and feasibility of Health Catch-UP! from staff and patient perspectives, and recommended Health Catch-UP! integration into routine care (e.g. NHS health checks) with an implementation package including staff and patient support materials, standardised care pathways (screening and catch-up vaccination, laboratory, and management), and financial incentivisation.

Conclusions

Clinical Decision Support Systems like Health Catch-UP! can improve disease detection and implementation of screening guidance for migrant patients but require robust testing, resourcing, and an effective implementation package to support both patients and staff.
Associations of periconception dietary glycemic index and load with fertility in women and men: a study among couples in the general population
Authors: Schipper Mireille C. , Boxem Aline J. , Blaauwendraad Sophia M. , Mulders Annemarie G. M. G. J. , Jaddoe Vincent W. V. , Gaillard Romy
Published: October 2024

Background

The dietary glycemic index (GI) and load (GL) reflect carbohydrate quality and quantity, potentially impacting fertility through modulation of insulin sensitivity and generation of oxidative stress. While fertility is influenced by both women and men, reproductive research often emphasizes maternal factors. We first examined periconception dietary intake in both women and male partners, and subsequent associations of dietary GI and GL with fecundability and subfertility.

Methods

Among 830 women and 651 male partners, participating in a population-based prospective cohort study from preconception onwards, we assessed periconception dietary intake and calculated GI and GL, using a food frequency questionnaire (FFQ) at median 12.4 weeks gestation (95% range 10.9, 18.4). Information on time to pregnancy was obtained through questionnaires, with subfertility defined as a time to pregnancy ≥ 12 months or use of assisted reproductive technology.

Results

In the periconception period, mean energy intake in women was 1870 kcal (SD: 500; 46% carbohydrates, 16% protein, 33% fat; dietary GI 56.2 (SD: 3.5) and GL 141.4 (SD: 67.4)). Mean energy intake in men was 2350 kcal (SD: 591; 43% carbohydrates, 16% protein, 33% fat; dietary GI 56.8 (SD: 3.2) and GL 156.7 (SD: 75.4)). Median time to pregnancy was 4.8 months (IQR: 1.2, 16.4), with 30.6% of 830 women experiencing subfertility. Dietary GI and GL were not associated with fertility outcomes in women. In men, higher dietary GI and GL across the full range were associated with decreased fecundability, after adjusting for socio-demographic and lifestyle factors, as well as dietary GI or GL of female partners [FR: 0.91, 95% CI 0.83, 0.99; FR: 0.90, 95% CI 0.81, 0.99, per SDS increase in dietary GI and GL, respectively]. When assessing the combined influence of dietary GI clinical categories in women and men, both partners adhering to a low GI diet tended to be associated with increased fecundability, but not with subfertility risk.

Conclusions

Suboptimal periconception carbohydrate intake may be negatively associated with male fertility, but not with fertility outcomes in women. Further studies are needed to assess whether a lower GI and GL diet is a feasible lifestyle intervention to improve couples fertility.
Enhancing Ras cheese safety: antifungal effects of nisin and its nanoparticles against Aspergillus flavus
Authors: Abd-Elhamed Esraa Y. , El-Bassiony Tawfik Abd El-Rahman , Elsherif Wallaa M. , Shaker Eman M.
Published: October 2024

Background

Due to the adverse effects of industrial chemicals and their carcinogenicity and toxicity for humans, the debates have increased on using natural preservatives. This study was conducted to investigate the inhibitory effect of pure nisin and nisin nanoparticles (nisin NPs) against Aspergillus flavus in vivo by inoculation in laboratory-manufactured Ras cheese. A novel, safe, and natural approach of nanoprecipitation using acetic acid was employed to prepare nisin nanoparticles. The prepared NPs were characterized using zeta-sizer, FTIR, and transmission electron microscopy (TEM). Furthermore, the cytotoxicity of nisin NPs on Vero cells was assessed. The minimum inhibitory concentrations (MICs) of nisin and its nanoparticles were determined in vitro against A. flavus isolates using the agar well-diffusion method. The sensory evaluation of manufactured Ras cheese was conducted over a 60-day storage period.

Results

The obtained results showed a strong antifungal activity of nisin NPs (0.0625 mg/mL) against A. flavus strain in comparison with pure nisin (0.5 mg/mL). Notably, the count decreased gradually by time from 2 × 108 at zero time and could not be detected at the 7th week. The count with pure nisin decreased from 2 × 108 at zero time and could not be detected at the 10th week where it’s enough time to produce aflatoxins in cheese. The MICs of nisin and nisin NPs were 0.25 and 0.0313 mg/mL, respectively. Nisin NPs used in our experiment had good biocompatibility and safety for food preservation. Additionally, the sensory parameters of the manufactured Ras cheese inoculated with nisin and nisin NPs were of high overall acceptability (OAA).

Conclusions

Overall, the results of this study suggested that adding more concentration (˃0.0625 mg/mL) from nisin nanoparticles during the production of Ras cheese may be a helpful strategy for food preservation against A. flavus in the dairy industry.
The multifaceted role of mitochondria in cardiac function: insights and approaches
Authors: Ravindran Sriram , Rau Christoph D.
Published: October 2024

Cardiovascular disease (CVD) remains a global economic burden even in the 21st century with 85% of deaths resulting from heart attacks. Despite efforts in reducing the risk factors, and enhancing pharmacotherapeutic strategies, challenges persist in early identification of disease progression and functional recovery of damaged hearts. Targeting mitochondrial dysfunction, a key player in the pathogenesis of CVD has been less successful due to its role in other coexisting diseases. Additionally, it is the only organelle with an agathokakological function that is a remedy and a poison for the cell. In this review, we describe the origins of cardiac mitochondria and the role of heteroplasmy and mitochondrial subpopulations namely the interfibrillar, subsarcolemmal, perinuclear, and intranuclear mitochondria in maintaining cardiac function and in disease-associated remodeling. The cumulative evidence of mitochondrial retrograde communication with the nucleus is addressed, highlighting the need to study the genotype-phenotype relationships of specific organelle functions with CVD by using approaches like genome-wide association study (GWAS). Finally, we discuss the practicality of computational methods combined with single-cell sequencing technologies to address the challenges of genetic screening in the identification of heteroplasmy and contributory genes towards CVD.
Rest the brain to learn new gait patterns after stroke
Authors: Krishnan Chandramouli , Augenstein Thomas E. , Claflin Edward S. , Hemsley Courtney R. , Washabaugh Edward P. , Ranganathan Rajiv
Published: October 2024

Background

The ability to relearn a lost skill is critical to motor recovery after a stroke. Previous studies indicate that stroke typically affects the processes underlying motor control and execution but not the learning of those skills. However, these studies could be confounded by the presence of significant motor impairments. Furthermore, prior research involving the upper extremity indicates that stroke survivors have an advantage in offline motor learning when compared with controls. However, this has not been examined using motor acuity tasks (i.e., tasks focusing on the quality of executed actions) that have direct functional relevance to rehabilitation.

Objective

Investigate how stroke affects leg motor skill learning during walking in stroke survivors.

Methods

Twenty-five participants (10 stroke; 15 controls) were recruited for this prospective, case-control study. Participants learned a novel foot-trajectory tracking task on two consecutive days while walking on a treadmill. The task necessitated greater hip and knee flexion during the swing phase of the gait. Online learning was measured by comparing tracking error at the beginning and end of each practice session, offline (rest-driven) learning was measured by comparing the end of the first practice session to the beginning of the second, and retention was measured by comparing the beginning of the first practice session to the beginning of the second. Online learning, offline learning, and retention were compared between the stroke survivors and uninjured controls.

Results

Stroke survivors improved their tracking performance on the first day (p = 0.033); however, the amount of learning in stroke survivors was lower in comparison with the control group on both days (p ≤ 0.05). Interestingly, stroke survivors showed higher offline learning gains when compared with uninjured controls (p = 0.011).

Conclusions

Even stroke survivors with no perceivable motor impairments have difficulty acquiring new motor skills related to walking, which may be related to the underlying neural damage caused at the time of stroke. Furthermore, stroke survivors may require longer training with adequate rest to acquire new motor skills.
Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury
Authors: Shan Xiao-Meng , Chen Chun-Wei , Zou Da-Wei , Gao Yan-Bin , Ba Yin-Ying , He Jia-Xin , Zhu Zhi-Yao , Liang Jia-Jun
Published: October 2024

Background

Tangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury.

Methods

The ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro.

Results

51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis.

Conclusion

TSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis.
Impact of a qualitative assessment approach for neonatal abstinence syndrome management: experience of a European reference center
Authors: Cortez Ferreira Mariana , Moura Figueiredo Ana , Pitorra Joaquim , Mesquita da Silva Joana
Published: October 2024

Background

The management of infants at risk of neonatal abstinence syndrome (NAS) remains challenging. In 2000 Maternidade Bissaya Barreto implemented a strategy based on the qualitative assessment of neonates and in 2018 the Eat, Sleep, Console (ESC) approach, a tool based on similar concepts, was created. The aim is to assess the efficacy of a qualitative assessment of infants at risk, compare it with the ESC approach and report temporal trends of NAS in a European hospital.

Methods

Retrospective cohort study of all infants of mothers with a history of drug abuse during pregnancy admitted to a tertiary European centre between January 2010 and December 2021. The therapeutical decision was guided by a qualitative assessment of the newborn’s well-being. The ESC approach was retrospectively determined. Pharmacologic treatment was used as a last resort. The clinical outcomes and therapeutic strategies employed were evaluated. Statistical association was evaluated. The incidence rate per 1000 births was calculated and temporal trend differences were identified.

Results

A total of 79 neonates at risk were included, of whom 40 (50.6%) developed NAS. Consolability was the most affected criterion (35.0%), followed by feeding difficulties (12.5%). Sleep was affected less frequently (5.0%). Overall, 37.5% of infants failed to meet at least one of the criteria. All neonates with a positive ESC failed the qualitative assessment (p = 1.000) After optimization of nonpharmacologic measures, drug therapy was still necessary in four cases (10.0% of infants with the syndrome). The incidence rate of NAS decreased from 3.9 per 1000 births in 2010 to 0.0 per 1000 births in 2021 (p = 0.025).

Conclusion

The qualitative assessment of the infant based on the ability to feed, sleep and be consoled correctly identified neonates at risk and led to a significant reduction in the use of drug therapy. The incidence rate of NAS decreased during the study period.
Paracetamol and ibuprofen fixed-dose combination for the management of acute mild-to-moderate pain in children: strengthening and enhancing of result of Nominal Group Technique through Delphi consensus
Authors: Castagno Emanuele , Parri Niccolò , D’Avino Antonio , Ferrari Elena , Marchisio Paola Giovanna , Messia Virginia , Taglialatela Maurizio , Staiano Annamaria
Published: October 2024

Background

Paracetamol and ibuprofen are the most commonly used drugs for pain treatment in children and their combination has shown improved analgesic effect compared to treatment with either drug alone. Current literature lacks specific guidelines regarding the settings in which this combination should be adopted.

Methods

The survey, conducted with Delphi methodology, involved 75 hospital and outpatient pediatricians with clinical experience in the management of pain in children. Pediatricians involved were asked to validate or not the results of the previous NominalGroup Tecnique (NGT) consensus and thus specify the optimal clinical settings in which the paracetamol/ibuprofen fixed-dose combination could be adopted.

Results

The results confirm the importance of the fixed-dose paracetamol and ibuprofen combination for the control of mild-to-moderate acute pain in children. Particularly, this association seems to be appropriate in case of headache, earache, odontalgia and musculoskeletal pain, and in specific settings such as post-operative and post-procedural pain. The broadening of the panel brought to slight variations in clinical management practices between hospital and outpatient specialists. Nonetheless, overall consensus supports the notion that the fixed dose combination is more efficacious than monotherapies and it is well tolerated. Moreover, experts unanimously agree on the usefulness of the combination for caregivers, leading to improved adherence and effectiveness.

Conclusions

Both the NGT consensus and the broader Delphi consensus confirm the usefulness of the paracetamol-ibuprofen fixed-dose combination in pediatric pain. This is attributed to its superior effectiveness compared to monotherapies, a good tolerability profile, and improved compliance and ease of use. Some pain settings related to chronic, inflammatory and rheumatological pathologies remain to be investigated to evaluate the use of this combination.
Bartonella infections are rare in blood-fed Ixodes scapularis and Ixodes pacificus ticks collected from rodents in the United States
Authors: Bai Ying , Osikowicz Lynn M. , Clark Jacoby , Foster Erik , Parise Christina , Maes Sarah , Eisen Rebecca J.
Published: October 2024

Background

Ixodes scapularis and Ixodes pacificus are important vectors of multiple pathogens in the United States. However, their role in transmission of Bartonella spp., which are commonly reported in rodents and fleas, has been debated. Our previous investigation on Bartonella spp. in host-seeking I. scapularis and I. pacificus showed Bartonella spp. were absent in the ticks, suggesting the two species are unlikely to contribute to Bartonella transmission. It is unclear whether the absence of Bartonella spp. in the host-seeking ticks was attributable to ticks not being exposed to Bartonella in nature or being exposed but unable to acquire or transstadially transmit the bacterium. To assess the likelihood of exposure and acquisition, we tested Ixodes spp. ticks collected from rodents for Bartonella infections.

Methods

Blood-fed I. scapularis ticks (n = 792; consisting of 645 larvae and 147 nymphs), I. pacificus ticks (n = 45, all larvae), and Ixodes angustus ticks (n = 16, consisting of 11 larvae and 5 nymphs) collected from rodents from Minnesota and Washington were tested for Bartonella spp. using a quadruplex polymerase chain reaction (PCR) amplicon next-generation sequencing approach that targets Bartonella-specific fragments on gltA, ssrA, rpoB, and groEL. In parallel, rodents and fleas collected from the same field studies were investigated to compare the differences of Bartonella distribution among the ticks, fleas, and rodents.

Results

Bartonella spp. were commonly detected in rodents and fleas, with prevalence of 25.6% in rodents and 36.8% in fleas from Minnesota; 27.9% in rodents and 45.2% in fleas from Washington. Of all tested ticks, Bartonella DNA was detected by gltA in only one larval I. scapularis tick from Minnesota.

Conclusions

The high prevalence of Bartonella spp. in rodents and fleas coupled with extremely low prevalence of Bartonella spp. in blood-fed ticks suggests that although Ixodes ticks commonly encounter Bartonella in rodents, they rarely acquire the infection through blood feeding. Notably, ticks were at various stages of feeding on rodents when they were collected. Laboratory transmission studies are needed to assess acquisition rates in fully blood-fed ticks and to assess transstadial transmission efficiency if ticks acquire Bartonella infections from feeding to repletion.

Graphical Abstract
Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome
Authors: Regmi S. , Ganguly A. , Pathak S. , Primavera R. , Chetty S. , Wang J. , Patel Shaini , Thakor A. S.
Published: October 2024

Background

Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”.

Method

This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs)  would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects.

Results

When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19.

Conclusion

Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.
Advancement in Multi-omics approaches for Uterine Sarcoma
Authors: Wang Wuyang , Hu Yu , Fu Fangfang , Ren Wu , Wang Tian , Wang Shixuan , Li Yan
Published: October 2024

Uterine sarcoma (US) is a rare malignant tumor that has various pathological types and high heterogeneity in the female reproductive system. Its subtle early symptoms, frequent recurrence, and resistance to radiation and chemotherapy make the prognosis for US patients very poor. Therefore, understanding the molecular mechanisms underlying tumorigenesis and progression is essential for an accurate diagnosis and targeted therapy to improve patient outcomes. Recent advancements in high-throughput molecular sequencing have allowed for a deeper understanding of diseases through multi-omics technologies. In this review, the latest progress and future potential of multi-omics technologies in US research is examined, and their roles in biomarker discovery and their application in the precise diagnosis and treatment of US are highlighted.
Targeting NOX2 and glycolytic metabolism as a therapeutic strategy in acute myeloid leukaemia
Authors: Ijurko Carla , Romo-González Marta , Prieto-Bermejo Rodrigo , Díez-Campelo María , Vidriales María-Belén , Muntión Sandra , Sánchez-Guijo Fermín , Sánchez-Yagüe Jesús , Hernández-Hernández Ángel
Published: October 2024

Acute myeloid leukaemia (AML) is a highly heterogeneous malignancy, with a poor 5-year overall survival rate of approximately 30%. Consequently, the search for novel therapeutic strategies is ongoing, and the identification of new vulnerabilities could accelerate progress. Oxidative stress and metabolic rewiring are established hallmarks of cancer, and recent evidence suggests that NADPH oxidases may regulate metabolism, potentially linking these two processes. Increasing research highlights the importance of NOX2 in AML, particularly its role in metabolic regulation. In this study, we investigated the effects of simultaneously inhibiting NOX2 and glycolysis in AML cells. Dual inhibition of NOX2 and glycolysis—by targeting hexokinase or lactate dehydrogenase (LDH)—significantly reduced cell proliferation, markedly impaired clonogenic potential, and induced extensive cell death in a broad panel of AML cell lines. Importantly, these findings were further validated in primary bone marrow samples derived from AML patients, where combined inhibition triggered similar potent anti-leukemic effects. Furthermore, the combined inhibition of NOX2 and LDH enhanced the efficacy of cytarabine (AraC), suggesting this approach could boost the effectiveness of conventional therapies. In an in vivo AML model, targeting NOX2 and LDH in myeloid progenitor cells delayed the onset of leukaemia and extended survival. In conclusion, our findings propose a novel therapeutic strategy for AML through the dual targeting of NOX2 and glycolysis.
The Effects of Aerobic Exercise Training on Testosterone Concentration in Individuals Who are Obese or Have Type 2 Diabetes: A Systematic Review and Meta-Analysis
Authors: Healy Rhiannon , Patten Rhiannon , Bauer Carlie , Woessner Mary N. , Bourke Matthew , Grossmann Mathis , Levinger Itamar
Published: October 2024

Background

Obesity and type 2 diabetes (T2D) are associated with alterations in testosterone concentrations. While evidence indicates that aerobic training can influence testosterone in healthy populations or females with hyperandrogenism, its impact in individuals with obesity or T2D remains unclear. Thus, the aim of this study was to investigate whether aerobic training can influence circulating testosterone concentrations in individuals with obesity or T2D.

Methods

EBSCOhost (CINAHL, MEDLINE, SPORTDiscus), PubMed and Embase were searched for articles published until August 2023. Eligible articles included individuals with obesity or T2D that underwent an aerobic exercise intervention with testosterone concentrations measured at baseline and post intervention. Two reviewers independently screened the seven articles included in this meta-analysis and conducted data extraction and risk of bias assessments.

Results

A total of 103 participants (62 men / 41 women) from three randomised controlled trials and four non-randomised controlled trials were included. Effect sizes were computed with random effects models. Aerobic exercise moderately increased testosterone concentrations in men (g = 0.565, 95% CI = 0.307 to 0.822, p < 0.001), but had no significant effect in women (g = -0.523, 95% CI = -1.541, 0.496, p = 0.314). Aerobic exercise had no significant effect on sex hormone-binding globulin or markers of insulin sensitivity (p > 0.05).

Conclusions

Aerobic training may be used to increase testosterone concentrations in men with obesity or T2D, but potentially has no influence in women. Given the low number of studies, further studies investigating the effect of exercise on circulating sex hormones in men and women with obesity or T2D are needed.
Sudden onset abdominal wall leakages of inguinal hernia in patients undergoing peritoneal dialysis: report of two cases with literature review
Authors: Banshodani Masataka , Kawanishi Hideki , Kajikawa Ryujiro , Shintaku Sadanori , Moriishi Misaki , Nishihara Masahiro , Tsuchiya Shinichiro
Published: October 2024

Background

In this report, we presented two cases of sudden onset abdominal wall leakages of inguinal hernia in patients undergoing peritoneal dialysis (PD).

Case presentation

A total of 519 patients with end-stage kidney disease underwent PD at our hospital between March 2006 and March 2023. Among them, 39 patients [7.5%; 36 men (92%); mean age, 66 years; median PD duration, 1.7 years] developed inguinal hernias, with an incidence rate of 0.85 per 100 dialysis patient-years. Two patients (0.4%; both men; age/PD duration, 65/4.6 years and 74/1.7 years) experienced sudden onset abdominal wall leakages of inguinal hernia, with a rupture rate of 0.04 per 100 dialysis patient-years. In these cases of sudden onset abdominal wall leakages, both patients underwent tension-free hernioplasty; one patient was shifted to hemodialysis due to discomfort experienced from the right groin to the thigh area, while the other patient remained on PD.

Conclusions

Clinicians should consider the possibility of sudden onset abdominal wall leakages of inguinal hernia in PD patients.
Usefulness of hot shot intermittent infusion online hemodiafiltration plus far-infrared therapy for dialysis patients with lower extremity arterial disease: a case report
Authors: Saito Makoto , Jingu Hiroomi , Oyama Yusuke , Tanaka Toshiyuki , Ohama Kazuya
Published: October 2024

Background

Lower extremity arterial disease (LEAD) occurs at a high frequency in dialysis patients and is associated with a poor prognosis. In recent years, intermittent infusion online hemodiafiltration (I-OHDF) combined with far-infrared therapy (FIR) has been reported as being useful in dialysis patients with LEAD. However, there are also reports of worsening of the ulcers and gangrene in some cases. Hot shot I-OHDF (HS I-OHDF), which involves intermittent infusion of heated dialysate, is reported as being more effective than conventional I-OHDF for improving the plasma refilling rate (PRR) and peripheral circulation. We report the case of a patient in whom a lower extremity ulcer healed only after we switched from I-OHDF + FIR to HS I-OHDF + FIR, and the usefulness of this treatment.

Case presentation

The patient was a 41-year-old male dialysis patient with LEAD who showed worsening of the ulcers in the lower extremity before he was switched from I-OHDF plus FIR to HS I-OHDF plus FIR; we compared the changes in the lower extremity blood flow, PRR, degree of wound healing, and subjective symptoms over time after the switch to HS I-OHDF plus FIR as compared with the values prior to the switching. As compared with the values during I-OHDF plus FIR, the lower extremity blood flow and PRR increased markedly during HS I-OHDF plus FIR. The wounds in the lower extremity improved over time during HS I-OHDF plus FIR and showed complete healing after 6 months; evaluation by visual analog scales (VASs) showed improved scores for all of fatigue, pain, coldness, and insomnia, and the patient reported improved subjective symptoms. The mechanism underlying the effectiveness of HS I-OHDF plus FIR in promoting wound healing is unknown, however, we speculated that the temperature change in the intermittent infusion solution resulted in increased blood flow in the true capillaries (resting vessels) and transfer of the nonthermal effects of FIR to more peripheral vessels.

Conclusions

This case demonstrates that combined use of HS I-OHDF with FIR can enhance the efficacy of FIR in dialysis patients with LEAD by increasing the lower extremity blood flow and PRR, which is useful for wound healing.
The potential of fibroblast growth factor-21 and adiponectin as diagnostic biomarkers for type 2 diabetes mellitus: differential levels in response to treatments
Authors: Al-Qusous Madleen Nabeel , Dwairi Rami , Hussein Rasha Mohamed
Published: October 2024

Background

Diabetes mellitus (DM) is a global epidemic disease affecting millions each year. Recent studies have suggested novel biomarkers that are linked to DM. This study aimed to measure the levels of fibroblast growth factor-21 (FGF-21) and adiponectin in the blood of patients with type 2 DM and to assess the variations in their levels in response to the type of treatments. The possible correlations with several biochemical parameters and the diagnostic potential of FGF-21 and adiponectin as biomarkers for DM were also investigated. Eighty subjects were classified into control, Type 2 DM patients who were treated with metformin, Type 2 DM patients who were treated with metformin + oral hypoglycemic agents (OHAs), and Type 2 DM patients who were treated with insulin + metformin + OHAs.

Results

The metformin + OHAs group and the insulin + metformin + OHAs group had higher levels of FGF-21 when compared to the control group. The metformin + OHAs also had significantly higher adiponectin levels when compared to the control or metformin groups. The serum levels of FGF-21 in the diabetic subjects were negatively correlated with LDL, direct bilirubin, albumin, and insulin levels and positively correlated with the duration of DM. However, the serum levels of adiponectin in the diabetic subjects were negatively correlated with weight while positively correlated with potassium levels. Remarkably, FGF-21 and adiponectin were effective biomarkers for diagnosing DM with a specificity of 100% and 90% and sensitivity of 52.3% and 64.5%, respectively.

Conclusion

These findings suggest that FGF-21 and adiponectin play crucial roles in DM diagnosis and prognosis and that their levels change depending on the treatment type.
Prevalence of central nervous system-active polypharmacy in a cohort of older adults in Argentina
Authors: Ferraris Augusto , Angriman Federico , Barrera Tomas , Penizzotto Paula , Faerman Sol , Rivadeneira Washington , Chiessa Alan , Mura Gaspar , Pollán Javier Alberto , Szmulewicz Alejandro G.
Published: October 2024

Background

Central nervous system (CNS)-active polypharmacy is frequent and potentially harmful in older patients. Data on its burden outside the USA and European countries remain limited.

Aims

To estimate the period prevalence of and factors associated with out-of-hospital CNS-active polypharmacy in older adults.

Method

We used data from a cohort of out-patients aged ≥60 years affiliated to the Hospital Italiano de Buenos Aires’ health maintenance organisation on 1 January 2021. A CNS-active polypharmacy event was defined as the concurrent exposure to ≥3 CNS-active medications (i.e. antidepressants, anti-epileptics, antipsychotics, benzodiazepines, Z-drugs and opioids) through filled out-of-hospital prescriptions. We calculated the period prevalence of CNS-active polypharmacy for 2021. We identified factors associated with CNS-active polypharmacy using a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals (CI).

Results

We included 63 857 patients. Pre-existing mental health diagnoses included anxiety (21%), depressive (14%) and sleep (11%) disorders. CNS-active polypharmacy occurred in 4535 patients, for a period prevalence of 7.1% (95% CI: 6.9–7.3%). The combination of an antidepressant, an antipsychotic and a benzodiazepine accounted for 21% of the CNS-active polypharmacy events. Frontotemporal dementia (odds ratio: 14.67; 95% CI: 4.47–48.20), schizophrenia (odds ratio: 7.93; 95% CI: 4.64–13.56), bipolar disorder (odds ratio: 7.20; 95% CI: 5.45–9.50) and depressive disorder (odds ratio: 3.50; 95% CI: 3.26–3.75) were associated with CNS-active polypharmacy.

Conclusions

One in 14 adults aged 60 years and older presented out-of-hospital CNS-active polypharmacy. Future studies should evaluate measures to reduce CNS-active medication use in this population.
RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial
Authors: Bonomi Marcelo , Blakaj D.M. , Sher David , Kabarriti Rafi , Colvett Kyle , Takiar Vinita , Bar-Ad Voichita , Goyal Sharad , Muzyka Brian , Niermann Kenneth , Abrouk Nacer , Oronsky Bryan , Reid Tony , Caroen Scott , Sonis Stephen
Published: October 2024

PURPOSE

Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities.

METHODS

PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method.

RESULTS

Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen.

CONCLUSION

This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.
Somatic DICER1-Mutant Benign Thyroid Nodules in Adults: A Group of Follicular Nodular Disease With Continuous Growth
Authors: Meng Lingyang , Li Haorong , Fu Yi’an , Yu Danyan , Tang Jiamin , Hu Yan , Fei Xiaochun , Yang Kaiyu , Liu Ziyuan , Peng Rongguang , Zhou Yulin , Wang Shu , Yan Jiqi , Shen Liyun , Han Rulai , Ye Lei
Published: October 2024

Context

Germline DICER1 mutations cause familial multinodular goiter (MNG). However, the prevalence of somatic DICER1 mutations in non-MNG benign thyroid nodules and their characteristics remain unknown.

Objective

To determine the prevalence of somatic DICER1-mutant non-MNG benign thyroid nodules and their clinicopathological, molecular, behavioral and transcriptional characteristics.

Methods

Adult-onset thyroid nodules with a pathological diagnosis were genotyped via targeted sequencing. DICER1-mutant nodules were assessed clinically and pathologically. Organoids were established to investigate follicular formation and growth. Transcriptomic analysis was conducted to evaluate transcriptional features, which were validated by immunofluorescence.

Results

Among 931 adult-onset thyroid nodules, we identified 13 benign thyroid nodules with DICER1 hotspot mutations. The majority harbored a somatic DICER1 hotspot mutation with a somatic DICER1 truncating variant. Clinically, 38.5% of the DICER1-mutant nodules exhibited substantial growth. DICER1-mutant nodules with durations longer than 2 years were substantially enlarged (P = .0448). Pathologically, all DICER1-mutant nodules were defined as thyroid follicular nodular disease (TFND). The TFND nodules with DICER1 mutations grew faster than those with wild-type DICER1. Organoid culture of a DICER1-mutant nodule revealed increased active follicular formation. Compared with the normal thyroid tissues, the DICER1-mutant nodules had similar thyroid differentiation scores, significantly higher extracellular signal-related kinase scores (P = .0141) and lower epithelial-mesenchymal transition scores (P = .0001). Moreover, the expression of genes related to follicular polarity, such as CDH16, SLC5A5, TSHR, and TPO, was downregulated in the DICER1-mutant nodules.

Conclusion

Somatic DICER1 2-hit mutations represent a notable percentage in adult patients with TFND, and DICER1-mutant benign thyroid nodules were characterized by continuous growth.
Associations of Phthalate Exposure With Adiposity and Metabolic Syndrome in US Adolescents and Adults, NHANES 2013 to 2018
Authors: Webb Mary D , Park Jee Won , Day Drew B , Trabulsi Jillian C , Sathyanarayana Sheela , Melough Melissa M
Published: October 2024

Context

Phthalates are ubiquitous endocrine-disrupting chemicals and suspected obesogens. However, the associations with fat distribution and associated cardiometabolic complications remain unclear.

Objective

We examined the associations between phthalate exposure, body fat (total and distribution patterns), and metabolic syndrome (MetS) among US adolescents and adults.

Methods

We analyzed cross-sectional data from 829 adolescents and 3905 adults in the 2013 to 2018 National Health and Nutrition Examination Survey. Total percentage body fat (%BF), visceral adipose tissue (VAT) mass, and android to gynoid (A/G) ratio were determined using dual-energy x-ray absorptiometry. Associations between molar sums of low molecular weight (∑LMW), high molecular weight (∑HMW), and di(2-ethylhexyl) phthalate (∑DEHP) metabolites, and adiposity indicators and MetS were analyzed with multivariable linear and logistic regressions. Models included sex interaction terms, were stratified by age group, and adjusted for relevant covariates.

Results

∑HMW and ∑DEHP exposures were positively associated with %BF in males, and all phthalate groups were associated with greater VAT mass and A/G ratio in adolescent males. Five-fold increases in ∑HMW and ∑DEHP metabolites were associated with 21.7% (95% CI, 10.5-33.9) and 18.0% (95% CI, 7.72-29.2) greater VAT mass among adolescent males, respectively. Sex modified the relationship between ∑HMW exposure and A/G ratio among adolescents (interaction P value = .0185). Phthalates were not associated with odds of MetS. When assessing individual MetS components, phthalates were associated with hyperglycemia in adult males.

Conclusion

Greater exposure to phthalates was associated with greater %BF in all males, and with fat distribution in adolescent males; however, phthalates were not linked to MetS.
Y box-binding protein 1 regulates zebrafish folliculogenesis partly through p21-mediated control of follicle cell proliferation
Authors: Zhu Bo , Zhang Zhiwei , Pardeshi Lakhansing , Chen Yingying , Ge Wei
Published: October 2024

Y box-binding protein 1 (Ybx1/ybx1) regulates gene expression through DNA/RNA binding. In zebrafish, Ybx1 is highly abundant in primary growth (PG) follicles in the ovary, but decreases precipitously as the follicles enter the secondary growth (SG). To understand Ybx1 function in folliculogenesis, we created a ybx1 mutant using TALEN and observed disrupted folliculogenesis during the previtellogenic (PV) to early vitellogenic (EV) transition of SG, resulting in underdeveloped ovaries and infertility. Expression and western blot analyses revealed differential gene expression between ybx1−/− and control ovaries, with significantly increased expression of cdkn1a (p21), a cell cycle inhibitor, in ybx1−/− follicles. While cdkn1a knockout via CRISPR/Cas9 was embryonically lethal, the heterozygote (cdkn1a+/−) displayed advanced follicle activation and maturation, contrasting with the ybx1−/− phenotype. Partial loss of p21 alleviated the ybx1−/− phenotype, restoring folliculogenesis with normal PG-PV and PV-EV transitions in ybx1−/−;cdkn1a+/− mutants. While ybx1−/− mutant follicle cells displayed poor proliferation in vivo and in vitro, the cells from the ybx1−/−;cdkn1a+/− follicles resumed normal proliferation. In conclusion, Ybx1 is crucial for early folliculogenesis in zebrafish, potentially by repressing cdkn1a expression, either directly or indirectly.
On Optimal Scheduling
Authors: Eliaz Kfir , Fershtman Daniel , Frug Alexander
Published: October 2024

We consider a decision-maker sequentially choosing among alternatives when periodic payoffs depend on both chosen and unchosen alternatives in that period. We show that when flow payoffs are the sum or product of payoffs from chosen and unchosen alternatives, the optimal policy is an index policy. We characterize key properties of the optimal dynamics and present an algorithm for computing the indices explicitly. Furthermore, we use the results to generalize Weitzman’s (1979) classic “Pandora’s boxes” problem to allow for complementarities. We illustrate the framework’s usefulness through applications, including decision problems with disappearing alternatives, repeated bargaining, dynamic supervision, and dynamic occupational choice. (JEL C78, D82, M11)
Retos de la paz total en Colombia
Authors: Gómez-Gómez Juan Fernando , González David Mendieta
Published: October 2024

Objetivo: Una de las grandes apuestas del Gobierno de Gustavo Petro es alcanzar lo que él ha llamado “la Paz Total”. El presente escrito se ocupará de los retos que puedan surgir en una negociación con las denominadas BACRIM, en un país que cuenta con varios grupos al margen de la ley que le han impedido tener un único modelo de justicia transicional, lo que ha llevado a considerar diferentes fórmulas para alcanzar la tan anhelada paz.
Metodología: Para la elaboración de este artículo científico sobre los retos de la Paz Total en Colombia, especialmente con las denominadas BACRIM, se utilizó un enfoque cualitativo con base en la revisión documental y el análisis crítico de fuentes secundarias. El proceso metodológico incluyó la identificación y selección de documentos clave, como leyes, decretos, informes oficiales, y estudios académicos relevantes sobre las políticas de paz implementadas en Colombia en los últimos años. Se realizó una contextualización de la justicia transicional y del acuerdo de paz con las FARC, lo que permitió evaluar las particularidades y desafíos actuales de la política de Paz Total.
Resultado: Se puedo concluir que el presidente Petro deberá aterrizar las ideas de su propuesta de “Paz Total” a la realidad cotidiana de las regiones en el marco de la arquitectura institucional y jurídica vigente, a fin de visibilizar la viabilidad y sostenibilidad del proyecto y que, transcurrida la mitad del mandato presidencial, cada vez se hace más difícil que el Presidente pueda materializar su gran promesa de paz para Colombia.
Contribuciones: El Gobierno Nacional deberá diseñar la esperada Ley de Sometimiento a la Justicia para los grupos armados, las organizaciones delincuenciales y demás actores que se pretendan vincular a los procesos derivados del proyecto de Paz Total. Igualmente, deberá construir una estrategia masiva en diferentes niveles para el despliegue pedagógico de lo que significa y lo que pretende el proyecto de Paz Total, en aras de que todos los sectores sociales y políticos tengan suficiente claridad sobre sus alcances prácticos.