bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the roadblocks: exploring substance use disorder treatment policies in Iran through a qualitative lens
Authors: Mirzaei Saeid , Yazdi-Feyzabadi Vahid , Mehrolhassani Mohammad Hossein , Nakhaee Nouzar , Oroomiei Nadia
Published: November 2024

Background

Different countries, including Iran, have implemented various policies to address substance use disorder. This study aims to describe the policies related to substance use disorder treatment and identify challenges related to these policies in Iran since the beginning of the Iranian Revolution in 1979.

Methods

This qualitative study utilized document analysis and interviews with policymakers and implementers. We reviewed a total of 22 documents related to substance use disorder treatment and harm reduction. The results from document analysis complemented and validated the interview data. The research population comprised policymakers and implementers, including individuals directly involved in formulating and implementing substance use disorder treatment policies. Purposive sampling was employed, with a snowball strategy utilized to maximize diversity. Data saturation was achieved after conducting 32 semi-structured interviews. Conventional content analysis was used for data analysis.

Results

In general, the policy landscape for substance use disorder treatment in the Islamic Republic of Iran can be divided into two periods: the “Moral Model” era (1979–1993) and the “Disease Model” era (1993–present). Challenges within the content of substance use disorder treatment policies in Iran encompass the lack of law revisions, existence of contradictions in laws and nature of disease, the absence of evidence-based policymaking, and an inadequate comprehensive perspective on the phenomenon of substance use disorder.

Conclusions

The presence of multiple authorities with different perspectives on substance use disorder and its treatment, coupled with the application of personal preferences in policymaking and the absence of evidence-based policymaking, have contributed to weaknesses in decision-making and policy formulation. The true philosophy of Disease Model appears not to have been fully grasped by health policymakers in Iran, as all Disease Model policies have been pursued with an emphasis on abstinence and quitting. Iran and other nations facing similar challenges should place more reliance on evidence-based approaches and shift away from the “Moral Model” paradigm to develop more effective substance use disorder treatment policies.
Critical decisions at the early stage of start-ups: a systematic literature review
Authors: González M Marcos Antonio , Terzidis Orestis , Lütz Phillip , Heblich Benedict
Published: November 2024

This systematic literature review (SLR) identifies and ranks the decisions that can be considered critical for entrepreneurs at the early stage of the start-up process. The sample (N = 56) derived from the SLR contained primary publications from the A + and A journals of the VHB-Journal ranking. Deductive and inductive approaches were used to define the critical decision domains. Then, the relevance of the domains was evaluated using the frequency of the selected studies. A key implication for founders is to understand that not all decisions that could be taken in the early stage may be critical for success. Most critical seems to invest time and effort in the, what we label the internal business and human core (Core People and Product Definition) and the external business and human core (Market segment selection and Partnerships). This study depicts an integrated view of the fragmented field of critical decisions in the context of early-stage start-ups by using a SLR. Thus, it creates value for theory-building and practitioners in entrepreneurship and innovation.
Dietary bile acids supplementation protects against Salmonella Typhimurium infection via improving intestinal mucosal barrier and gut microbiota composition in broilers
Authors: Hu Dan , Yang Xiaoran , Qin Ming , Pan Li’an , Fang Haiyan , Chen Pengnan , Ni Yingdong
Published: November 2024

Background

Salmonella Typhimurium (S. Typhimurium) is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms. As signaling molecules regulating the interaction between the host and gut microbiota, bile acids (BAs) play a protective role in maintaining gut homeostasis. However, the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored. Therefore, the aim of this study was to investigate the potential role of feeding BAs in protecting against S. Typhimurium infection in broilers.

Methods

A total of 144 1-day-old Arbor Acres male broilers were randomly assigned to 4 groups, including non-challenged birds fed a basal diet (CON), S. Typhimurium-challenged birds (ST), S. Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection (ST-ANT), and S. Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs (ST-BA).

Results

BAs supplementation ameliorated weight loss induced by S. Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers (P < 0.05). Compared to the ST group, broilers in ST-BA group had a higher ileal mucosal thickness and villus height, and BAs also ameliorated the increase of diamine oxidase (DAO) level in serum (P < 0.05). It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells (GCs) were increased in the ST-BA group, consistent with the upregulation of MUC2 gene expression in the ileal mucosa (P < 0.05). Moreover, the mRNA expressions of Toll-like receptor 5 (TLR5), Toll-like receptor 4 (TLR4), and interleukin 1 beta (IL1b) were downregulated in the ileum by BAs treatment (P < 0.05). 16S rDNA sequencing analysis revealed that, compared to ST group, BAs ameliorated the decreases in Bacteroidota, Bacteroidaceae and Bacteroides abundances, which were negatively correlated with serum DAO activity, and the increases in Campylobacterota, Campylobacteraceae and Campylobacter abundances, which were negatively correlated with body weight but positively correlated with serum D-lactic acid (D-LA) levels (P < 0.05).

Conclusions

Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota, which eventually relieves the damage to the intestinal barrier and weight loss induced by S. Typhimurium infection in broilers.
Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience
Authors: Melzer Michael Karl , Ma Yanchun , Lindenmayer Jessica , Morgenstern Clara , Wezel Felix , Zengerling Friedemann , Günes Cagatay , Gaisa Nadine Therese , Kleger Alexander , Bolenz Christian
Published: November 2024

Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice.
A 18F-FDG PET/CT-based deep learning-radiomics-clinical model for prediction of cervical lymph node metastasis in esophageal squamous cell carcinoma
Authors: Yuan Ping , Huang Zhen-Hao , Yang Yun-Hai , Bao Fei-Chao , Sun Ke , Chao Fang-Fang , Liu Ting-Ting , Zhang Jing-Jing , Xu Jin-Ming , Li Xiang-Nan , Li Feng , Ma Tao , Li Hao , Li Zi-Hao , Zhang Shan-Feng , Hu Jian , Qi Yu
Published: November 2024

Background

To develop an artificial intelligence (AI)-based model using Radiomics, deep learning (DL) features extracted from 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/Computed Tomography (PET/CT) images of tumor and cervical lymph node with clinical feature for predicting cervical lymph node metastasis (CLNM) in patients with esophageal squamous cell carcinoma (ESCC).

Methods

The study included 300 ESCC patients from the First Affiliated Hospital of Zhengzhou University who were divided into a training cohort and an internal testing cohort with an 8:2 ratio. Another 111 patients from Shanghai Chest Hospital were included as the external cohort. For each sample, we extracted 428 PET/CT-based Radiomics features from the gross tumor volume (GTV) and cervical lymph node (CLN) delineated layer by layer and 256 PET/CT-based DL features from the maximum cross-section of GTV and CLN images We input these features into seven different machine learning algorithms and ultimately selected logistic regression (LR) as the model classifier. Subsequently, we evaluated seven models (Clinical, Radiomics, Radiomics-Clinical, DL-Clinical, DL-Radiomics, DL-Radiomics-Clinical) using Radiomics features, DL features and clinical feature.

Results

The DL-Radiomics-Clinical (DRC) model demonstrated higher AUC of 0.955 and 0.916 compared to the other six models in both internal and external testing cohorts respectively. The DRC model achieved the highest accuracy among the seven models in both the internal and external test sets, with scores of 0.951 and 0.892, respectively.

Conclusions

Through the combination of Radiomics features and DL features from PET/CT imaging and clinical feature, we developed a predictive model exhibiting exceptional classification capabilities. This model can be considered as a non-invasive method for predication of CLNM in patients with ESCC. It might facilitate decision-making regarding to the extend of lymph node dissection, and to select candidates for postoperative adjuvant therapy.
Volumetric changes of porcine collagen matrix and free gingival grafts for soft-tissue grafting to increase the width of keratinized tissue around dental implants: a retrospective clinical study
Authors: Ramanauskaite Ausra , Müller Katharina Melissa , Schliephake Carla , Obreja Karina , Begic Amira , Dahmer Iulia , Parvini Puria , Schwarz Frank
Published: November 2024

Aim

To compare three-dimensional changes of aporcine derived collagen matrix (CM) and free gingival grafts (FGG) for increasing keratinized tissue (KT) at dental implants over a 24-month follow-up period.

Materials and methods

This retrospective study enrolled 25 patients exhibiting 41 implants with deficient KT width (i.e., < 2 mm) who underwent soft tissue augmentation using either CM (11 patients/15 implants) or FGG (14 patients/26 implants). The primary outcome was tissue thickness change (mm) at treated implant sites between 1- (S0), 12- (S1), and 24-months (S2). Secondary outcome was the changes of KT width over a 24-month follow-up period.

Results

Dimensional analyses from S0 to S1 and from S0 to S2 revealed a mean decrease in tissue thickness of -0.05 ± 0.35 mm and − 0.31 ± 0.41 mm in the CM group, and − 0.23 ± 0.38 mm and − 0.22 ± 0.81 mm in the FGG group, with no significant differences found between the groups (S0-S1: p = 0.14, S0-S2: p = 0.58). Within S1 and S2, the CM and FGG groups displayed comparable tissue thickness reduction (CM: -0.32 ± 0.53 mm, FGG: -0.02 ± 0.21 mm; p = 0.07). The FGG group exhibited a significantly greater KT gain 24-months compared to the CM group (CM: 1.50 ± 1.14 mm, FGG: 4.04 ± 1.65 mm; p < 0.001).

Conclusions

CM and FGG were associated with comparable three-dimensional thickness changes over a period of 24 months. A significantly wider KT band could be established in the FGG group.

Graphical Abstract
Patient perception of bowel urgency and remission in moderately to severely active Crohn’s disease or ulcerative colitis: a qualitative study
Authors: Gibble Theresa Hunter , Stassek Larissa , Harding Gale , Stefan Marissa , Fikre Tsion , Bleakman Alison Potts , Moses Richard , Dubinsky Marla
Published: November 2024

Background

Bowel urgency, the sudden and immediate need to have a bowel movement, is common in patients with ulcerative colitis (UC) and Crohn’s disease (CD). While its impact in UC is well established, less is known about its importance in CD. Further, what level of bowel urgency control patients with UC or CD would consider to be acceptable or in remission has not been established. This qualitative study aimed to understand perceptions of bowel urgency and remission in these patients.

Methods

Semi-structured combined concept elicitation and cognitive interviews were conducted to explore how adults with moderate-to-severe UC or CD and current or recent bowel urgency think about the concept of bowel urgency and its remission. The Urgency Numeric Rating Scale (UNRS) was used to examine different levels of bowel urgency severity and to investigate what level of bowel urgency patients would consider as representing remission.

Results

Forty adults (n = 19 UC, n = 21 CD) recruited from six US sites completed the study. Sociodemographic and clinical characteristics were similar in both groups. Both groups reported impacts of bowel urgency on physical, social, professional, and emotional aspects of their lives. Most participants (n = 15 UC, n = 18 CD) reported having experienced one or more incidents of urgency-related fecal incontinence. Most participants considered remission to be a state with a normal or reduced number of bowel movements and no or less frequent bowel urgency, and they noted that remission would increase their ability to engage in daily activities without fear of fecal incontinence. Participants were able to map different levels of severity of bowel urgency to UNRS score ranges (scale: 0–10), and they indicated that a mean UNRS score of 5 (UC) or 4 (CD) would be the highest point on the NRS at which they would still consider their bowel urgency to be in remission.

Conclusions

Bowel urgency is an important issue for patients with either moderate-to-severe UC or CD, and its remission would improve their lives. Further, these patients may still consider bowel urgency to be in remission even at UNRS scores as high as 4 or 5.
Efficiency of the fungi isolated from the tomato rhizosphere to control the north root-knot nematode Meloidogyne hapla Chitwood 1949
Authors: Nekoval Svetlana N. , Chernyakovich Maxim N. , Churikova Arina K. , Maskalenko Oksana A. , Muravyov Vyacheslav S.
Published: November 2024

Background

In the South of Russia, due to the large acreage of tomato crops (Solanum lycopersicum Mill.), there is an acute problem of plant protection against the obligate endoparasitic of the root system Meloidogyne hapla Chitwood 1949. The aim of this study was to assess the nematicidal activity of fungal strains isolated from the rhizosphere of tomato plants infected with root-knot nematodes (RKN) (Meloidogyne spp.).

Results

After conducting route surveys, 10 soil samples were selected from the rhizosphere of tomato plants affected by RKN. Fifteen isolates of fungi belonging to different species were isolated from the soil samples. The species composition of the isolated fungal strains was determined: Metarhizium anisopliae IG01, Penicillium citrinum IG02, Trichoderma harzianum IG03, Aspergillus niger IG04, Trichoderma ghanense IG05, Trichoderma harzianum IG06, Trichoderma atroviride IG07, Aspergillus awamori IG08, Trichoderma atroviride IG09, Paramyrothecium roridum IG10, Trichoderma atroviride IG11, Trichoderma hamatum IG12, Beauveria bassiana IG13, Aspergillus ochraceus IG14, Purpureocillium lilacinum IG15. After initial screening in the laboratory, strains with the greatest nematicidal activity and safe for humans were selected: M. anisopliae ИГ01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09. The mortality rate of RKN when using these fungal strains varied from 79.4 ± 1.8 to 93.9 ± 3.1%. In the greenhouse, the fungal strains M. anisopliae IG01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09 showed high results in reducing the number of galls on the roots of tomato plants, and their biological efficacy was 71.4–83.0%.

Conclusion

Work on the study of the nematicidal activity of fungi, in vitro and in vivo, allows us to conclude that strains isolated from the rhizosphere of plants can be effective in combating the north RKN (M. hapla). In the future, it is planned to establish the compatibility of M. anisopliae IG01, T. harzianum IG03, T. ghanense IG05, T. atroviride IG07, T. atroviride IG09 with each other and selecting the ratios of the studied strains to obtain mixtures to create an effective biological nematicide.
Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients
Authors: Jendretzky Konstantin Fritz , Lezius Lisa-Marie , Thiele Thea , Konen Franz Felix , Huss André , Heitmann Lena , Güzeloglu Yunus Emre , Schwenkenbecher Philipp , Sühs Kurt-Wolfram , Skuljec Jelena , Wattjes Mike Peter , Witte Torsten , Kleinschnitz Christoph , Pul Refik , Tumani Hayrettin , Gingele Stefan , Skripuletz Thomas
Published: November 2024

Background

Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.

Methods

In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.

Results

We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.

Conclusion

Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.
JCCG ALL-B12: Evaluation of Intensified Therapies With Vincristine/Dexamethasone Pulses and Asparaginase and Augmented High-Dose Methotrexate for Pediatric B-ALL
Authors: Kato Motohiro , Okamoto Yasuhiro , Imamura Toshihiko , Kada Akiko , Saito Akiko M. , Iijima-Yamashita Yuka , Deguchi Takao , Ohki Kentaro , Fukushima Takashi , Anami Kenichi , Sanada Masashi , Taki Tomohiko , Hashii Yoshiko , Inukai Takeshi , Kiyokawa Nobutaka , Kosaka Yoshiyuki , Yoshida Nao , Yuza Yuki , Yanagimachi Masakatsu , Watanabe Kenichiro , Sato Atsushi , Imai Chihaya , Taga Takashi , Adachi Souichi , Horibe Keizo , Manabe Atsushi , Koh Katsuyoshi
Published: November 2024

PURPOSE

The JCCG ALL-B12 clinical trial aimed to evaluate the effectiveness of unvalidated treatment phases for pediatric ALL and develop a safety-focused treatment framework.

PATIENTS AND METHODS

Patients age 1-19 years with newly diagnosed B-ALL were enrolled in this study. These patients were stratified into standard-risk (SR), intermediate-risk (IR), and high-risk (HR) groups. Randomized comparisons assessed the effectiveness of vincristine (VCR)/dexamethasone pulses in the SR group, evaluated the effects of L-asparaginase (ASP) intensification in the IR group, and compared standard consolidation including block-type treatment with experimental consolidation with high-dose methotrexate (HD-MTX) intensified with VCR and ASP in the HR group.

RESULTS

Of 1,936 patients enrolled, 1,804 were eligible for the experimental treatment. The overall 5-year event-free survival and overall survival rates were 85.2% (95% CI, 83.5 to 86.8) and 94.3% (95% CI, 93.1 to 95.3), respectively. The cumulative incidence of relapse and postremission nonrelapse mortality was 13.2% (95% CI, 11.6 to 14.8) and 0.6% (95% CI, 0.3 to 1.0), respectively. Random assignment in the SR group showed no significant benefit from pulse therapy. In the IR group, ASP intensification had limited effects. In the HR group, standard block therapy and HD-MTX yielded equivalent outcomes.

CONCLUSION

The ALL-B12 trial achieved favorable outcomes in a nationwide cohort by stratifying treatment on the basis of risk and balancing treatment intensity. This study not only demonstrated that existing standard of care can be further refined but also indicated that improvement in outcomes with intensified chemotherapy has reached a plateau.
Understanding the Biology and Testing Techniques for Pharmacogenomics in Oncology: A Practical Guide for the Clinician
Authors: Steuerwald Nury M. , Morris Sarah , Nguyen D. Grace , Patel Jai N.
Published: November 2024

Pharmacogenomic (PGx) testing is a growing area of personalized medicine with demonstrated clinical utility in improving patient outcomes in oncology. PGx testing of pharmacogenes affecting drug pharmacokinetics, pharmacodynamics, and response can help inform drug selection and dosing of several anticancer therapies and supportive care medications. Several PGx testing techniques exist including polymerase chain reaction (PCR), MassARRAY, microarray, and sequencing. This review article provides a clinician-friendly guide of these techniques. Understanding the advantages, limitations, ideal use, and potential clinical applications of each platform can help clinicians choose the appropriate PGx testing platform for specific use cases.
Current Clinical Utility of Circulating Tumor DNA Testing in Breast Cancer: A Practical Approach
Authors: Xi Jing , Ma Cynthia X. , O'Shaughnessy Joyce
Published: November 2024

Circulating tumor DNA (ctDNA) refers to DNA fragments released from cancer cells into the bloodstream. Clinical utility of ctDNA in breast cancer has been explored in both metastatic breast cancer (MBC) and early-stage breast cancer (EBC) settings. In MBC, ctDNA can detect therapeutically targetable genomic alterations and has shown great potential in predicting treatment response or resistance. Accumulating data suggest that ctDNA might also have prognostic value in MBC. In EBC, emerging data have shown ctDNA's predictive and/or prognostic value in both neoadjuvant and adjuvant settings. Minimal residual disease (MRD) detection via ctDNA to detect clinical recurrence after curative therapy is a rapidly advancing field. In this review, we discuss the existing and emerging data regarding ctDNA utility in both MBC and EBC settings.
Blood Pressure Decreases in Overweight Elderly Individuals on Vitamin D: A Randomized Trial
Authors: Rahme Maya , Al-Shaar Laila , Tamim Hani , El-Hajj Fuleihan Ghada
Published: November 2024

Context

Evidence for a beneficial role of vitamin D on blood pressure (BP) outcomes is inconclusive.

Objective

This work aimed to investigate the effect of 2 doses of cholecalciferol (vitamin D3) supplementation coadministered with calcium on systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Methods

Exploratory analyses were conducted from a 1-year, multicenter, double-blind, randomized controlled trial (RCT). Total of 221 ambulatory older overweight individuals received calcium dose and oral vitamin D3, at the equivalent of 600 IU/day or 3750 IU/day.

Results

SBP and DBP decreased significantly in the overall group, and in the high-dose group at 6 and 12 months. Similar trends were observed in the low-dose group, but did not achieve statistical significance. In participants with a body mass index (BMI) greater than 30, SBP decreased significantly in both treatment groups whereas DBP significantly decreased in the high-dose group only. In the subgroups of hypertensive participants (N = 143), there was a decrease in SBP and DBP at 6 and 12 months, with both vitamin D doses and independently of BMI levels. Using multivariate linear mixed models with random effects in the overall group of participants, SBP at 6 and 12 months was significantly predicted by BMI (β = .29; P = .05) and by baseline SBP (β = .16; P < .001), but not by vitamin D treatment dose.

Conclusion

Vitamin D and calcium decrease SBP and DBP in overweight older individuals, but more is not necessarily better. This effect is seen in individuals with BMI greater than 30, in hypertensive patients, and seems to be largely independent of dose.
Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol
Authors: Newell-Price John , Fleseriu Maria , Pivonello Rosario , Feelders Richard A , Gadelha Mônica R , Lacroix André , Witek Przemysław , Heaney Anthony P , Piacentini Andrea , Pedroncelli Alberto M , Biller Beverly M K
Published: November 2024

Purpose

To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Methods

Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.

Results

Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, −7.4%/−4.9%, −6.0%/−5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, −5.0%, −4.8%, and 1.9%; glycated hemoglobin, −5.1%, −4.8%, and −1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.

Conclusion

In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.

Clinical trial identifiers

NCT02180217 (LINC 3); NCT02697734 (LINC 4)
Direct Aspiration Versus Combined Technique for Anterior Distal, Medium Vessel Occlusions Stroke: The JET Distal Vessel Occlusion Study
Authors: Palmisano Vitanio , Simonetti Luigi , Marotti Nicola , Reverberi Lorenzo , Comai Alessio , Ganimede Maria Porzia , Comelli Simone , Taglialatela Francesco , Zini Andrea , Paolucci Matteo , Sponza Massimo , Ciardi Chiara , Verganti Luca , Vallone Stefano , Gorgatti Tommaso , Franchini Enrica , Marrazzo Antonio , Paladini Andrea , della Malva Giuseppina , Barone Michele , Briatico Vangosa Alessandra , Di Stasi Carmine , Burdi Nicola , Semeraro Vittorio
Published: November 2024

BACKGROUND AND OBJECTIVES:

The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs.

METHODS:

We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated.

RESULTS:

A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004).

CONCLUSION:

In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter.
Assessment of potential drug-drug interactions in hospitalized patients with infectious diseases: an experience from a secondary care hospital
Authors: Shareef Javedh , Sridhar Sathvik Belagodu , Ahmad Ismail Abu Nawa , Rao Padma G.M. , Ain Ur Rashid
Published: November 2024

Background Polypharmacy is common among hospitalized patients with infectious infections owing to comorbidities or concomitant illnesses. This raises the likelihood of drug-drug interactions and creates uncertainty for healthcare providers. This study aimed to assess the potential drug-drug interactions (pDDIs) among hospitalized patients with infectious diseases in a secondary care hospital. Methods A prospective observational study was conducted in the internal medicine ward for six months after the ethics committee’s approval. Data were collected from patient case records, and prescriptions were screened for pDDIs from a portable electronic physician information database (PEPID) resource analyzed using SPSS, version 27.0. Results In total, 148 patient case records were analyzed, and 549 pDDIs were identified, with 66.8% having at least one or more DDIs. The mean number of drug interactions was 3.70 ± 4.58 per prescription. The most frequently encountered drug interactions were drug combinations such as bisoprolol with atorvastatin and aspirin with tazobactam/piperacillin. Bivariate analysis showed that age, comorbidities, length of hospital stay, and the number of drugs prescribed were risk factors associated with DDIs (p<0.05). In the multiple binary logistic regression analysis, DDIs were significantly associated with comorbidities and the number of prescribed medications (p<0.0001). Conclusions This study observed the prevalence of DDIs in hospitalized patients with infectious diseases of ‘moderate’ severity. Prescription screening using a drug information database assists in early identification and prevention of DDIs, enhancing drug safety and quality of patient-centered care.
The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort
Authors: Naceur Ines , Baya chatti Amal , Jridi Maysam , Ben Achour Tayssir , Smiti Monia , Said Fatma
Published: November 2024

Background Inflammatory idiopathic myopathies (IIM) are a heterogeneous group of complex connective tissue diseases (CTD), primarily characterized by inflammatory involvement of skeletal muscles. Several other organs may also be affected, including lungs, heart, skin, gastrointestinal tract, and joints. Objective Describe the clinical and immunological characteristics of IIM among Tunisian patients. Method A retrospective study conducted in the internal medicine department at the Rabta Hospital over 22 years, including adult patients with IIM according to the ACR/EULAR classification criteria, and anti-synthetase syndrome (ASS) according to Connors’ criteria. Inclusion body myositis was excluded. Demographic, clinical, and immunological characteristics were analyzed. Results Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). The ACR/EULAR criteria enabled the inclusion of 88% of the patients. Dermatomyositis (DM) was the most frequent entity (47%), followed by Polymyositis (PM) (36%) and Amyotrophic dermatomyositis (ADM) (4%). Connors criteria allowed the inclusion and classification with ASS of 33 patients, including those excluded by the ACR/EULAR criteria (12%). Muscular involvement was present in 88% of patients, affecting locomotor (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) muscles. Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. ILD was reported across all subgroup: ASS (85%), PM (57%), DM (17%), and ADM (100%). NSIP was the most common radiologic pattern (59%). Skin involvement (85%), consistently present in DM and ADM, affected 91% of ASS patients. Joint involvement (48%) was predominantly polyarticular (68%). Myositis-specific antibodies (MSAs) were detected in 52% of patients, with a predominance of anti-synthetase antibodies (ASAs). Another CTD was noted in 24% of patients and cancer in 17% of patients. Conclusion Our study underscored the clinical diversity among IIM patients and the systemic nature of these diseases, where muscular involvement is not always uniform.
Understanding the future of dengue in Malaysia: Assessing knowledge, attitude, and homeowner practices in mitigating climate-driven risks
Authors: Andoy-Galvan Jo Ann , Patil Sapna Shridhar , Wong Yin How , Madhavan Priya , Wee Lei Hum , Chong Pei Pei , Looi Chung Yeng , Shaik Imam , Ponnupillai Anitha , Hasamnis Ameya Ashok , Bhargava Prabal , Mugilarasi Arasarethinam , Wong Eng Hwa , Yeong Chai Hong , Yau Weng Keong , Dinesh Mahalingam , Venugopalan Kulankara Balan , Muhamad Nor Asiah , Ma’amor Nur Hasnah , Rosli Izzah Athirah , Leman Fatin Norhasny
Published: November 2024

Introduction Dengue fever poses a significant public health threat, particularly in tropical regions like Malaysia. The rising incidence of dengue outbreaks challenges healthcare systems and highlights the urgent need for effective preventive measures. Climate change, with rising temperatures and shifting rainfall patterns, is expected to worsen the dengue situation in the coming years. Methods . This is a cross-sectional study conducted among adult residents of low-cost housing apartments in an urban poor community in Kuala Lumpur, Malaysia involving approximately 16,000 residents. A representative sample of 1,636 residents was calculated using the Krejcie and Morgan formula, and stratified random sampling was used to ensure proportional representation across the various floors of each PPR community apartment block. Data were collected using a structured questionnaire adapted from a validated Malay version. The questionnaire assessed respondents’ knowledge, attitudes, and practices (KAP) related to dengue prevention, categorising KAP scores as “Good” (≥80%) or “Poor” (<80%). Descriptive statistics summarized population characteristics and KAP scores, while logistic regression identified predictors of KAP levels, with significance set at p ≤ 0.05. Results In this community, 76.7% of participants exhibited poor knowledge and 83.1% had a negative attitude towards dengue, despite 66.7% demonstrating good preventive practices. The PPR location significantly predicts dengue knowledge, attitudes, and preventive practices, with p-values of less than 0.001 for all domains. Marital status also predicts dengue knowledge (p = 0.007) and preventive practices (p = 0.023), while prior infection with dengue is a predictor of preventive practices (p = 0.047). Conclusion Despite the community’s good dengue prevention practices, likely influenced by environmental expectations, there remains a critical need for education to sustain and strengthen these efforts, as climate change continues to worsen in the coming years. It is crucial to help residents grasp the relevance of these practices, so they can apply them more effectively as climate-driven risks intensify. Targeted interventions should de designed differently for each of the four PPR communities as their levels of knowledge, attitude and practices vary significantly, taking into account independent factors like marital status and prior dengue infection, which shape preventive behaviors.
The complete mitogenome of an unidentified Oikopleura species
Authors: Wibisana Johannes Nicolaus , Plessy Charles , Dierckxsens Nicolas M. , Masunaga Aki , Miao Jiashun , Luscombe Nicholas
Published: November 2024

Appendicularians are planktonic tunicates abundant all over the world. Currently, only two complete annotated mitochondrial genome assemblies are available for appendicularians, both for cryptic species of Oikopleura dioica. This underrepresentation of available appendicularian mitochondrial genomes limits environmental DNA sequencing (eDNA) studies that rely on mitochondrial markers as a taxonomic barcode. We report the complete mitochondrial genome assembly and annotation of an unknown appendicularian species isolated from the Amami Oshima island, Kagoshima prefecture, Japan, that has significant sequence difference with other currently available assemblies and will serve as a useful resource for ecological studies and further mitochondrial studies of appendicularians.
“Transgenders are not dinosaurs!” Stigma faced by transgender women in their daily lives in India: implications for research and policy
Authors: Yatirajula Sandhya Kanaka , Mukherjee Ankita , Giri Santosh , Maulik Pallab K
Published: November 2024

Background Transgender women face stigma that adversely impacts their mental wellbeing. The stigma can be self-directed (internal), discrimination, violence and hatred directed towards them by others, mostly cis-gender persons (interpersonal stigma) and discrimination faced at the level of institutional arrangements (structural stigma). Methods This was an exploratory study that used qualitative methods of data collection (focused group discussions and in-depth interviews) to gather data from consenting adult trans women who lived in the city of Kolkata situated in the eastern state of West Bengal in India. Results The findings showed that trans women faced the trauma of non-acceptance and even rejection by their families when they began to express their chosen gender. Their gender non-conforming behaviour made them the butt of ridicule and harassment in school, resulting in many of them not finishing school. This made finding employment difficult. The trans women study participants also faced harassment at the hands of the police and from hospital staff, making them reluctant to approach the police for help and seek treatment from health providers for their physical as well as mental health concerns. Conclusions It is important for researchers to be cognizant of the challenges faced by trans women/transgender people while designing and conducting research. It is also important for policymakers to make gender affirming policies to mitigate and eliminate the stigma that transgender people are subject to thereby promoting their wellbeing.
Association between type 2 diabetes and periodontitis: a population-based study in the North Peru
Authors: Mayta-Mayorga Marcela , Guerra-Rodríguez Victoria , Bernabe-Ortiz Antonio
Published: November 2024

Background Periodontitis, one of the most common forms of periodontal disease, has been linked to several cardiovascular factors including metabolic syndrome and inflammatory processes. This study aimed to determine the association between type 2 diabetes mellitus (T2DM) and periodontitis in a representative sample of individuals in the north of Peru. Materials and methods Secondary data analysis using information of a population-based survey, enrolling subjects aged 35 to 69 years. The outcome was periodontitis, evaluated using a self-reported and validated 8-item questionnaire, whereas the exposure was the presence of T2DM, evaluated using results of oral glucose tolerance test and categorized into two different forms: (a) normoglycemic, prediabetes, and T2DM, and (b) without T2DM, with T2DM and <5 years of diagnosis, and with T2DM and ≥5 years of diagnosis. Poisson regression models were utilized to report prevalence ratios (PR) and 95% confidence intervals (95% CI). Results Data from 1606 individuals were analyzed, with a mean age of 48.2 (SD: 10.6) years, and 50.3% were women. Of these, 272 (16.9%) had prediabetes and 176 (11.0%) had T2DM (17.3% with <5 years of disease). Overall, 97.0% presented at least one symptom compatible with periodontitis, 882 (55.0%) had mild, 643 (40.0%) had moderate, and 5% had severe periodontitis. In multivariable model, those with T2DM had a higher prevalence of periodontitis (PR = 1.99; 95% CI: 1.12 - 3.54). Similarly, those with <5 years of disease had a higher prevalence of periodontitis (PR = 2.48; 95% CI: 1.38 - 4.46). Conclusions Our research confirms the association between T2DM and periodontitis, especially among those with recent diagnosis (<5 years). Symptoms of periodontitis are quite common in our study population. Our results suggest a need to periodically assess oral health in patients with T2DM.
Neuroblastoma cell lines display heterogeneity in differentiation responses
Authors: Ferguson Kirsty M. , Gillen Sarah L. , Abou Grealy Fiona M. Y. , Vedi Aditi , Philpott Anna
Published: November 2024

Background Neuroblastoma is the most common extra-cranial childhood solid tumour, arising during development from stalled neural crest-derived precursor cells. In a subset of children younger than 18 months of age, neuroblastoma can undergo spontaneous regression driven by differentiation, leading to great interest in developing differentiation therapies to re-direct neuroblastoma cells down their correct developmental pathway. Recently, we have shown that combinatorial treatment with the CDK4/6 inhibitor palbociclib and differentiation-inducing agent retinoic acid inhibits proliferation and drives neuronal differentiation of adrenergic-type neuroblastoma cell lines. Methods Here, we explore the differentiation potential of neuroblastoma cell lines in vitro in response to palbociclib and retinoic acid treatment using microscopy, transcriptomic and qRT-PCR analyses. Results We present evidence suggesting that neuroblastoma cells can give rise to mixtures of neural crest-derived adrenal gland cell types, and that differentiation responses correspond to changes in patterns of extracellular matrix substrate expression. Conclusions This study builds a case to further investigate and consider heterogeneity in neuroblastoma cell differentiation and the role of the extracellular matrix in these cell fate decisions.
A range of voltage-clamp protocol designs for rapid capture of hERG kinetics
Authors: Lei Chon Lok , J Whittaker Dominic , J Windley Monique , D Perry Matthew , P Hill Adam , R Mirams Gary
Published: November 2024

We provide details of a series of short voltage-clamp protocols designed for gathering a large amount of information on hERG (Kv11.1) ion channel gating. The protocols have a limited number of steps and consist only of steps and ramps, making them easy to implement on any patch clamp setup, including automated platforms. The primary objective is to assist with parameterisation, selection and refinement of mathematical models of hERG gating. We detail a series of manual and automated model-driven designs, together with an explanation of their rationale and design criteria. Although the protocols are intended to study hERG1a currents, the approaches could be easily extended and generalised to other ion channel currents.
Navigating stress, anxiety, and mentorship: Challenges for students working on dissertations in the pandemic era
Authors: He Chen Yu
Published: November 2024

PhD students often encounter significant challenges, stress, and anxiety throughout their academic journey, particularly in their final year. This study explores the common difficulties faced by PhD students conducting thesis research at Chinese universities, focusing on their experiences with online supervision during the COVID-19 pandemic. A survey was conducted with ten full-time PhD students from selected Chinese universities, utilizing a combination of scaled, closed, and open-ended questions. The results indicate that students faced considerable challenges during online supervision, mainly due to inadequate funding and irregular, delayed supervisor feedback. Significant sources of stress and anxiety included thesis writing, supervisor relationships, and socioeconomic issues. However, adequate supervision, timely feedback, and purposeful guidance were found to mitigate these challenges. The study concludes that online supervision during the pandemic has intensified the difficulties faced by PhD students, negatively impacting the quality of their research and completion rates. To improve the supervision process, students recommended enhancing communication, increasing supervisor accessibility, and providing prompt feedback to support timely dissertation completion.