bluuebunny/crossref_metadata_2025 huggingface dataset:
The genomic landscape of the immune system in lung cancer: present insights and continuing investigations
Authors: Roshan-Zamir Mina , Khademolhosseini Aida , Rajalingam Kavi , Ghaderi Abbas , Rajalingam Raja
Published: June 2024

Lung cancer is one of the most prevalent malignancies worldwide, contributing to over a million cancer-related deaths annually. Despite extensive research investigating the genetic factors associated with lung cancer susceptibility and prognosis, few studies have explored genetic predispositions regarding the immune system. This review discusses the most recent genomic findings related to the susceptibility to or protection against lung cancer, patient survival, and therapeutic responses. The results demonstrated the effect of immunogenetic variations in immune system-related genes associated with innate and adaptive immune responses, cytokine, and chemokine secretions, and signaling pathways. These genetic diversities may affect the crosstalk between tumor and immune cells within the tumor microenvironment, influencing cancer progression, invasion, and prognosis. Given the considerable variability in the individual immunegenomics profiles, future studies should prioritize large-scale analyses to identify potential genetic variations associated with lung cancer using highthroughput technologies across different populations. This approach will provide further information for predicting response to targeted therapy and promotes the development of new measures for individualized cancer treatment.
Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors
Authors: Paudel Siddhi N. , Hutzen Brian J. , Miller Katherine E. , Garfinkle Elizabeth A. R. , Chen Chun-Yu , Wang Pin-Yi , Glaspell Andrea M. , Currier Mark A. , Ringwalt Emily M. , Boon Louis , Mardis Elaine R. , Cairo Mitchell S. , Ratner Nancy , Dodd Rebecca D. , Cassady Kevin A. , Cripe Timothy P.
Published: June 2024

Introduction

Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness.

Methods

Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy’s antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others.

Results

Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment.

Discussion

In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.
Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38
Authors: Li Song , Chen Dianze , Yang Yanan , Guo Huiqin , Liu Dandan , Sun Nana , Bai Xing , Wang Kaili , Li Tengfei , Li Guanghui , Yang Chunmei , Zhang Wei , Zhang Li , Zhao Gui , Peng Liang , Liu Sijin , Tu Xiaoping , Zhang Ruliang , Tian Wenzhi
Published: June 2024

Background

CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).

Methods

Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.

Results

Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.

Conclusion

A panel of BsAbs targeting CD38 and CD47 developed based on the “mAb-tarp” platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.
Identification of Anaplasma marginale adhesins for bovine erythrocytes using phage display
Authors: Noh Susan M. , Ujczo Jessica , Alperin Debra C.
Published: June 2024

Bovine anaplasmosis, caused by Anaplasma marginale, is one of the most common tick-borne diseases of cattle and has a worldwide distribution. The high costs of bovine anaplasmosis are due to treatment, decreased production, and outbreaks resulting in high mortality. The impact of bovine anaplasmosis is greatest in tropical and subtropical regions where tick vectors are abundant year around. Prevention generally relies on the use of tetracyclines to prevent disease and acaricides to reduce tick burdens. Thus, additional methods to prevent disease while reducing the use of antibiotics are needed. Protection can be reliably achieved with immunization using outer membrane proteins, thus allowing for the possibility for development of a recombinant vaccine. However, prioritizing the selection and testing of antigens from the protective outer membrane extract remains a challenge. Because A. marginale is an obligate intracellular pathogen, surface proteins that mediate adhesion to host cells, primarily red blood cells (RBCs), are functionally relevant vaccine candidates. With some exceptions, the proteins that bind RBCs remain unknown. To address this gap, a phage display library expressing 66 A. marginale proteins was screened to identify adhesins for bovine RBCs. Of the screened proteins, 73% were eliminated due to poor binding to RBCs. Several potential adhesins were identified, including Msp1b and OmpA, which are known adhesions for bovine RBCs and tick cells, respectively. Additionally, Mlp3, Am779, Msp3, and Omp13 met the criteria as RBCs adhesins and may serve as high priority vaccine candidates for future testing.
Microbiome and metabolome analyses reveal significant alterations of gut microbiota and bile acid metabolism in ETEC-challenged weaned piglets by dietary berberine supplementation
Authors: Nie Xiaoyan , Lu Qi , Yin Yucheng , He Zhentao , Bai Yinshan , Zhu Cui
Published: June 2024

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1β and IL-8 mRNA expression in piglets challenged with ETEC K88 (p < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration (p < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment (p < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) as well as the colonic mRNA expression of FXR, fibroblast growth factor19 (FGF19), takeda G protein-coupled receptor 5 (TGR5) and organic solute transporters beta (OST-β) in piglets (p < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets (p < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5, Occludin, TFF3, and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration (p < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration (p < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets.
Dynamic off-resonance correction improves functional image analysis in fMRI of awake behaving non-human primates
Authors: Shahdloo Mo , Khalighinejad Nima , Priestley Luke , Rushworth Matthew , Chiew Mark
Published: June 2024

Introduction

Use of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data.

Methods

We correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction.

Results

Applying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates.

Conclusions

Our results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.
Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise
Authors: Lee Earric , Nissinen Tuuli A. , Ylä-Outinen Laura , Jalkanen Aaro , Karppinen Jari E. , Vieira-Potter Victoria Jeanne , Lipponen Arto , Karvinen Sira
Published: June 2024

Introduction

Estrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon.

Methods

We studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n = 64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography.

Results

OVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p ≤ 0.005). OVX reduced maximal running capacity by 17% (p = 0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p = 0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p ≤ 0.024).

Discussion

Our results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.
Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial
Authors: Cao Wei-Yi , Liu Jun-Yu , Sun Min , Wang Jing-Kun , Lu Fang , Yang Qiao-Ning , Zhang Wan-Tong , Zi Ming-Jie , Zhang Bai-E , Liu Hong-Bin , Wang Shu-Ge , Wu Yi , Wu Rong-Zu , Wu Wen-Di , Li Rui , Zhu Zhao-Yun , Gao Rui
Published: June 2024

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation.

Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method.

Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed.

Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism.

Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.
The role of lactate-induced protein lactylation in gliomas: implications for preclinical research and the development of new treatments
Authors: Liu Xiaoying , Zhou Yue , Wang Haichuan
Published: June 2024

The most prevalent primary brain tumors in adults are gliomas. In addition to insufficient therapeutic alternatives, gliomas are fatal mostly due to the rapid proliferation and continuous infiltration of tumor cells into the surrounding healthy brain tissue. According to a growing body of research, aerobic glycolysis, or the Warburg effect, promotes glioma development because gliomas are heterogeneous cancers that undergo metabolic reprogramming. Therefore, addressing the Warburg effect might be a useful therapeutic strategy for treating cancer. Lactate plays a critical role in reprogramming energy metabolism, allowing cells to rapidly access large amounts of energy. Lactate, a byproduct of glycolysis, is therefore present in rapidly proliferating cells and tumors. In addition to the protumorigenesis pathways of lactate synthesis, circulation, and consumption, lactate-induced lactylation has been identified in recent investigations. Lactate plays crucial roles in modulating immune processes, maintaining homeostasis, and promoting metabolic reprogramming in tumors, which are processes regulated by the lactate-induced lactylation of the lysine residues of histones. In this paper, we discuss the discovery and effects of lactylation, review the published studies on how protein lactylation influences cancer growth and further explore novel treatment approaches to achieve improved antitumor effects by targeting lactylation. These findings could lead to a new approach and guidance for improving the prognosis of patients with gliomas.
Leadership as a determinant of need fulfillment: implications for meta-theory, methods, and practice
Authors: Pincus J. David
Published: June 2024

Of all the most prominent business concepts (e.g., DE&I, employee well-being, employee engagement, organizational culture, etc.) none rivals leadership in terms of public interest and annual monetary investment. Despite the obvious importance of leadership as a determinant of many important outcomes, the concept of leadership has been surprisingly hard to pin down, lacking consensus as to its precise meaning. As numerous authors introduce ever more constructs (e.g., servant leadership, toxic leadership, sustainable leadership, transformational leadership, etc.), the leadership concept has become emblematic of the problem of construct proliferation. Like the related fields of employee engagement, subjective well-being, and organizational culture, the leadership field is in desperate need of a clearly articulated meta-theory to house its many constructs, allowing theory and measurement to build up instead of continuing to pile up. This paper argues for grounding the concept of leadership within the psychological literature on human needs. In reviewing the leading definitions of leadership in the literature we find that they are reducible to a core set of follower needs that can be facilitated or inhibited by leaders. We propose that there is substantial value in adopting a comprehensive needs-based taxonomy over current approaches. We consider the impact of setting the concepts of leadership within existing need constructs for each of the following: (a) theory, especially the development of leadership frameworks and particularly how the concept of leadership relates to the concepts of organizational culture, employee well-being, and employee engagement; (b) methods, including the value of applying a comprehensive, structured model; and (c) practice, where we emphasize the practical advantages of clear operational definitions.
Distribution of self-reported borderline personality disorder traits symptoms in a large-scale clinical population
Authors: Lin Yong , Guo ZiLei , Zhou Yong , Wei YanYan , Xu LiHua , Tang XiaoChen , Wang Zixuan , Hu YeGang , Wang JiJun , Mei Yi , Wu HaiSu , Luo YanLi , Zhang TianHong
Published: June 2024

Introduction

Borderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations.

Methods

A total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: “F1: Affective Instability and Impulsivity”, “F2: Interpersonal Unstable and Extreme Reactions”, and “F3: Identity Disturbance”.

Results

Among 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p<0.001).

Discussion

Our study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.
Litigation in access to universal health coverage for children and adolescents in Brazil
Authors: Coelho Tavares da Silva Suely , Tavares da Silva Paulo Henrique , Antão de Medeiros Robson , Barbosa do Nascimento Vânia
Published: June 2024

Background

Brazil’s Unified Health System (SUS) ensures universal, equitable, and excellent quality health coverage for all. The broad right to health, supported by the Constitution, has led to excessive litigation in the public sector. This has negatively impacted the financial stability of SUS, created inequality in children and adolescents’ access to healthcare, and affected communication between the healthcare system and the judiciary. The enactment of Law Number 13.655 on 25 April 2018, proposed significant changes in judicial decisions. This study aimed to investigate decision-making changes in health litigation involving children and adolescents following the implementation of the new normative model.

Methods

The study is cross-sectional, analyzing 3753 national judgment documents from all State Courts of Brazil, available on their respective websites from 2014 to 2020. It compares regional legal decisions before and after the promulgation of Law Number 13.655/2018. Data tabulation, statistical analysis, textual analysis, coding, and counting of significant units in the collected documents were performed. The results of data cross-referencing are presented in tables and diagrams.

Results

The majority (96.86%) of legal claims (3635 cases) received partial or total provision of what was prescribed by the physician. The Judiciary predominantly handled these cases individually. The analysis indicates that the decisions made did not adhere to the norms established in 2018.

Conclusion

Regional heterogeneity in health litigation was observed, and there was no significant variability in decisions during the studied period, even after the implementation of the new normative paradigm in 2018. Technical-scientific support was undervalued by the magistrates. Prioritizing litigants undermines equity in access to Universal Health Coverage for children and adolescents.
Prevention method preferences and factors influencing hypothetical choice among women in South Africa: a survey exploring opportunities for a multipurpose prevention technology implant
Authors: Martin Catherine E. , Kutywayo Alison , Mataboge Paballo , Chidumwa Glory , Mthimkhulu Nqaba , Bothma Rutendo , Mullick Saiqa
Published: June 2024

Introduction

South African women bear an intersecting burden of HIV, sexually transmitted infections (STIs) and unintended pregnancy. Multipurpose prevention technologies (MPTs) are a class of products that address multiple needs and have the potential to improve uptake and use of prevention products.

Methods

Analysing survey data from 703 HIV-negative women 18–40 years in three provinces in South Africa, collected between July and November 2022, this study explores their preferences for prevention methods and factors influencing choice of hypothetical prevention methods, including MPTs. Descriptive statistics and multinomial regression analyses were conducted to determine prevention method preferences and factors associated with choosing a pill, injectable or MPT-implant type prevention method.

Results

Most women wanted to prevent HIV, STIs and pregnancy. The most important factors when choosing a prevention product were whether it provided dual and long-term protection and if side effects were manageable. If choosing only one method, half of women would choose any MPT-implant and a quarter each would choose a pill or an injectable method, with method choices differing by population group.

Discussion

Prevention method choices were influenced by sexual-behavioural factors and current and prior contraceptive method use. Providing a choice of prevention methods and a population specific approach to new method development and introduction with access to accurate information could enhance their ability to fill a gap in prevention needs.
Determinants of climate change adaptation strategies and intensity of use; micro level evidence from crop farmers in Kenya
Authors: Ndiwa Aurillia Manjella , Mburu John , Mulwa Richard , Chumo Chepchumba
Published: June 2024

Climate change and its negative impacts pose a threat to crop production in Kenya. However, climate change adaptation strategies have the potential to address the challenges faced by crop farmers. Despite this, there is limited literature to inform policy on the best interventions to help farmers deal with climate issues. This study assessed the determinants of climate change adaptation strategies and the intensity of their use among 723 crop farmers in Busia County, Kenya, selected through a multistage sampling technique. Data were collected using a structured questionnaire and analyzed using principal component analysis (PCA), multinomial logit regression, and the ordered probit model. The climate change adaptation strategies were categorized into crop diversity, cover crops, use of drought-resistant crops, and irrigation. According to the results, the factors contributing to the uptake of the different adaptation strategies were age, household size, access to credit, training access, off-farm income, group membership, frequency of receiving climate change information, and extension services. The major factors influencing the uptake of multiple climate change adaptation strategies were access to credit and off-farm income. The study shows that certain adaptation strategies, such as using cover crops, do not require credit and offer an important option in an environment with limited resources. On the other hand, adaptation measures such as irrigation demand financial resources for farmers to implement them, highlighting the importance of information and awareness in adopting adaptation strategies and the supportive role of financial resources, particularly for adopting multiple strategies. Therefore, this study suggests implementing policies and interventions that encompass knowledge-based strategies such as extension services, training, climate change education, group participation, and financial mechanisms like income generation activities and access to credit. These integrated strategies will enable farmers to adopt various climate change adaptation methods for sustainable crop production.
Ultrasound-guided approach to surgery for nodal recurrence following lateral neck dissection for differentiated thyroid carcinoma. A single institution experience
Authors: Pacilli Mario , Pavone Giovanna , Quazzico Andrea , Fersini Alberto , Ambrosi Antonio , Tartaglia Nicola
Published: June 2024

Introduction

Total thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period.

Methods

From January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection.

Results

All surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations.

Conclusions

Surgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery.
Biomaterials in Regenerative Medicine
Authors: Malik Reem Javed
Published: June 2024

Physiological regenerative system of human body is incapable of restoring the function when an injury exceeds its normal limits. Conventional methods previously being used for repair and rejuvenation of tissues had certain limitations that have brought the biomaterials to the forefront in the area of regenerative medicine. Biomaterials provide optimal support to the tissue during the process of healing and remodeling. Numerous classes of biomaterials are focused on specific applications; most prominent among them are polymers. Biomaterials are now being used in several areas such as fabrication, hematology and blood cell substitutes, tissue engineering, extracorporeal artificial organs, bone and vascular regeneration, stem cell differentiation and soft tissue repair. However, for the success of biomaterials in regenerative medicine , the focus should not only be on the physical, mechanical and chemical properties of the materials but also the fundamental principles of biological interactions and biocompatibility.
Effects of Stationary Cycling on Spasticity and Range of Motion in Children with Diplegic Cerebral Palsy: A Quasi Interventional Study
Authors: Ghani Hafiza Muriam , Razzaq Maria , Safdar Nabeela , Umer Bilal , Tariq Fatima
Published: June 2024

Background: Literature shows that cerebral palsy becomes challenging disability with the passage of time. Various treatment protocols are used to treat balance and coordination problems during rehabilitation programs however effective techniques are still needed to address spasticity and limited range of motion.
Objectives: To determine the effects of stationary cycling on spasticity and range of motion in diplegic cerebral palsy children.
Methods: An interventional study design (Quasi study design) was conducted in Rising Sun Mughalpura branch and Compass Schools for Special Education Lahore in 6 months from Feb 2019 to Aug 2019, after approval of synopsis. 68children with Spastic Diplegic Cerebral Palsy meeting inclusion criteria were enrolled in the study. Sample size was estimated using formula for Sample Size determination in health studies version 2.0.21 WHO. The static bicycle was used as an intervention tool. Two readings were taken before and after treatment. The data was analyzed by using IBM SPSS 20. Qualitative variables age, weight, gender and height were expressed as percentages. As the data found was parametric with a homogenous impression, paired sample t test was used to compare mean score at pre-post levels for ashworth scale and range of motion at knee and ankle joints. A p value less than 0.05 were taken as significant. Ashwroth Scale was used for spasticity and for Range of Motion goniometer was used.
Results: The paired sample statistics of pre-post testing of Ashworth Scale Score for calf muscles (M= 1.02, SD= 0.79), while for hamstring muscles (M= 1.13 SD= 0.84) with the significant p value 0.00. Knee and ankle range was (M=9.70, SD= 0.54) and (M=0.82, SD= 2.69) respectively, with a significant p value 0.00 for both.
Conclusion: It is concluded that stationary cycling has significant role in decreasing spasticity and increasing range of motion in children with diplegic spastic cerebral palsy.
Postural Ergonomic Risk Assessment and Work-related Musculoskeletal Symptoms Among Surgeons
Authors: Riaz Huma , Khan Huma , Ain Qurat ul
Published: June 2024

Background: Work-related musculoskeletal disorders (WMSDs) develop mainly because of poor work ergonomics. Surgeons are much prone to develop the musculoskeletal symptoms due to the nature of their precise work linked with prolong postures.
Objectives: To assess the level of postural ergonomic risk exposure and frequency of work-related musculoskeletal symptoms among Surgeons.
Methods: This was an observational, descriptive cross-sectional survey conducted among surgeons (n=100) working in hospitals of Rawalpindi and Islamabad, Pakistan. Convenient sampling technique was used. Structured survey questionnaire was used to collect demographic data and work details of surgeons. Pre-validated tools such as Quick Exposure Check (QEC) and Body Mapping Tool were also used. SPSS version 21 was used for data entry and analysis.
Results: More than half of the surgeons’ working posture exposed them to high 49(49%) and very high ergonomic risk 15(15%). The mean of Quick Exposure Check score was 55.71±14. Majority of the surgeons 64(64%) requires urgent and immediate change of their work posture. A significant difference of QEC score (p= 0.001) between males and females was found. Statistically significant difference (p=0.002) of QEC score among Surgeons. 64(64%) of the participants have reported work-related body pain in lower back 35(35%), neck 29(29%), shoulder 16(16%), wrist 15(15%), ankle 15(15%), upper back 14(14%), hip pain 9(9%), knee 9(9%) and elbows 5(5%).
Conclusion: It is concluded that work- related posture puts surgeons at higher ergonomic risk. Most of them were experiencing work-related musculoskeletal pain in some of their body regions.
Online teaching self-efficacy of physical therapy educators in the wake of COVID-19 pandemic
Authors: Malik Arshad Nawaz , Jahan Saira
Published: June 2024

Background: Following COVID-19, higher educational institutions are advancing towards distance learning, which is a new experience for many educators. Self-efficacy is a cognitive trait related to perseverance and determination in overcoming the challenges.
Objective: To assess the level of virtual teaching self-efficacy of physical therapy academicians.
Methods: A descriptive cross-sectional study was conducted. All physical therapy educators who were offering online courses during the pandemic received a link to a web survey through Google forms. The Michigan Nurse Educator's Sense of Efficacy for Online Teaching instrument was implied to assess self-efficacy for teaching methods. Using a 32-items MNESEOT scale, study respondents were asked to rate their responses to questions about teaching methods on a Likert scale ranging over 'nothing' (1) to 'a great deal' (9). Mean scores were computed for every participant for different domains of instructional strategies, classroom management, student participation, and computer skills.
Results: Faculty who were asked how effective they felt teaching online stated that they were most effective when using computers and instructional strategies (7.0), followed by classroom management (6.9) and student engagement (6.6) with a mean score of 27.50±4.7. Participants generally reported that they could prepare, conduct, and evaluate online courses to an extent greater than "some" to "quite a bit."
Conclusion: It is concluded that the self-efficacy of study participants in online instruction was quite high.
Stability Investigation of Fully Recycled Support System of Steel-Pipe-Anchored Sheet Pile in Soft Soil Excavation
Authors: Li Peng , Wu Gang , Yang Junjie , Liu Qiang
Published: June 2024

As a temporary project, the supporting system of excavation often encounters issues such as the waste of support components, environmental pollution, and high carbon emissions. This article presents a foundation pit support technology that utilizes steel tube anchorage sheet piles, which can be assembled and fully recycled. The composition of the support system is also introduced. Furthermore, a large-scale model test of steel-pipe-anchored sheet piles was designed and implemented. The displacement of each component of system and stability during excavation were investigated using 3D finite element modeling and analysis. The study results indicate that the deformation and failure mode of the model foundation under the steel-pipe-anchored sheet pile support system are closely related to the distance between the pipe pile and the sheet pile. When the distance is 10 cm, both the pipe pile and the sheet pile tilt simultaneously. When the distance is approximately 30–50 cm, the sliding surface becomes exposed from the position of the pipe pile. At distances up to 100 cm, the sliding surface is exposed between the pipe pile and the sheet pile. The anchoring effect of pipe piles and tie rods can effectively reduce the horizontal displacement of the sheet pile itself. The horizontal displacement at the top of both the pipe pile and sheet pile remains consistent throughout the excavation period of this model foundation. During excavation, measured earth pressure on the sheet pile is less with theoretical active earth pressure. After excavation, the maximum horizontal displacement of the top of the pipe pile exhibits a hyperbolic relationship with excavation depth.
Transcriptome Study in Sicilian Patients with Autism Spectrum Disorder
Authors: Salemi Michele , Schillaci Francesca A. , Lanza Giuseppe , Marchese Giovanna , Salluzzo Maria Grazia , Cordella Angela , Caniglia Salvatore , Bruccheri Maria Grazia , Truda Anna , Greco Donatella , Ferri Raffaele , Romano Corrado
Published: June 2024

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term “Response to Oxygen-Containing Compound”. Additionally, the GO Cellular Component pathway “Mitochondrion” stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD.
Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling
Authors: Su Yueqing , Cao Chenyun , Chen Shiyan , Lian Jiamei , Han Mei , Liu Xuemei , Deng Chao
Published: June 2024

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks’ treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.
Gender-Related Difference in Skin Oxygenation in Young Patients with Uncomplicated Type 1 Diabetes
Authors: Neubauer-Geryk Jolanta , Myśliwiec Małgorzata , Bieniaszewski Leszek
Published: June 2024

Gender, through genetic, epigenetic and hormonal regulation, is an important modifier of the physiological mechanisms and clinical course of diseases. In diabetes mellitus, there are gender differences in incidence, prevalence, morbidity, and mortality. This disease also has an impact on the microvascular function. Therefore, this cross-sectional study was designed to investigate how gender affects the cutaneous microcirculation. We hypothesized that gender should be an important factor in the interpretation of capillaroscopy and transcutaneous oxygen saturation results. The study group consisted of 42 boys and 55 girls, uncomplicated diabetic pediatric patients. Females (F) and males (M) did not differ in terms of age, age at onset of diabetes, or diabetes duration. Furthermore, they did not differ in metabolic parameters. The comparison showed that group F had lower BP, higher pulse, and higher HR than group M. Group F had significantly lower creatinine and hemoglobin levels than group M. In children and adolescents with type 1 diabetes without complications, there was a gender difference in microcirculatory parameters. The resting transcutaneous partial pressure of oxygen was significantly higher in females than in males. However, there were no gender-related differences in basal capillaroscopic parameters or vascular reactivity during the PORH test. Our results indicate that studies investigating the structure and function of the microcirculation should consider the role of gender in addition to known cofactors such as puberty, body mass index, physical activity, and cigarette smoking.