bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing vaccine uptake in sub-Saharan Africa: a collaborative COVID-19 vaccination campaign in Madagascar using an adaptive approach
Authors: Pavoncello Viola , Kislaya Irina , Andrianarimanana Diavolana Koecher , Marchese Valentina , Rakotomalala Rivo , Rasamoelina Tahinamandranto , Veilleux Simon , Guth Ariane , Zafinimampera Alexina Olivasoa Tsiky , Ratefiarisoa Sonya , Totofotsy Olivette , Doumbia Cheick Oumar , Rakotonavalona Rivomalala , Ramananjanahary Holinirina , Randriamanantany Zely Arivelo , May Jürgen , Rakotoarivelo Rivo Andry , Puradiredja Dewi Ismajani , Fusco Daniela
Published: January 2025

Background

The COVID-19 pandemic has highlighted the need for more effective immunization programs, including in limited resource settings. This paper presents outcomes and lessons learnt from a COVID-19 vaccination campaign (VC), which used a tailored adaptive strategy to optimise vaccine uptake in the Boeny region of Madagascar.

Methods

Guided by the Dynamic Sustainability Framework (DSF), the VC implementation was regularly reviewed through multi-sectoral stakeholder feedback, key informant interviews, problem-solving meetings, and weekly monitoring of outcome indicators to identify and apply key adaptations. Qualitative data on processes were collected and analysed using a rapid assessment approach. Outcome indicators, including pre- and post-VC vaccine hesitancy and trends in vaccine doses administered, were analysed using generalized linear models. Additionally, vaccination coverage, geographic reach, and target population characteristics, and sustainability indicators, such as staff trained, facilities equipped, and degree of integration of operational and educational materials were also tracked.

Results

Key strategy adaptations included using a proactive campaign approach, community-led awareness and outreach, particularly in remote areas, and addressing cold chain, waste management, vaccine transport, and information technology (IT) equipment gaps. Over six months, 24,888 COVID-19 vaccines were administered. The adapted strategy led to an 8% increase in doses administered weekly (RR = 1.08, CI 95%: 1.01-1.15). However, vaccine hesitancy among the unvaccinated population remained unchanged (∆ = 0.02, CI 95%: -0.04-0.08). In terms of sustainability, 340 staff were trained, and 10 primary healthcare facilities were equipped and refurbished.

Conclusions

Implementing collaborative, multi-sectoral vaccination strategies that integrate healthcare services with proactive outreach and community-driven campaigns are effective in increasing vaccine coverage in resource-limited settings. It demonstrates how theory-based adaptive strategies can enhance vaccination rates, even if they do not significantly impact COVID-19 vaccine hesitancy within the community. More generally, this initiative has important implications for adult vaccination programmes other than those related to COVID-19.
Study protocol for a hybrid type 3 effectiveness-implementation trial of a team-based implementation strategy to support educators’ use of a social engagement intervention
Authors: Locke Jill , Sridhar Aksheya , Shih Wendy , Shire Stephanie , Eisman Andria B. , Kim Emily , Du Adora , Espeland Christine , Kasari Connie
Published: January 2025

Background

Remaking Recess (RR) is a school-based evidence-based peer social engagement intervention for autistic students. RR involves direct training and coaching with educators; however, educators face several barriers to implementation at both the individual- and organizational-levels. This protocol paper describes a multi-site study that will test whether an educator-level implementation strategy, coaching, with or without a school-level implementation strategy, school-based teams, will maximize educators’ use (fidelity and sustainment) of RR for autistic students and their peers who are socially-isolated, rejected, or peripheral and may need additional support during recess.

Methods

This study will employ a hybrid type-3 effectiveness-implementation trial. Fifty-five elementary schools will be recruited as well as 121 educators (e.g., classroom assistants, aides), 55 general and special educator teachers, and 83–138 other school personnel (e.g., administrators). Additionally, at least 118 autistic students and allistic or non-autistic classmates will be recruited as RR recipients. Participants will complete baseline assessments at the beginning of the year, and all schools will be provided RR training. Schools will be randomized to coaching with or without school-based teams. This study will measure RR fidelity (primary outcome), RR sustainment, as well as peer engagement, social network inclusion, and social skills (secondary outcomes). It is expected that coaching with school-based teams will improve both RR fidelity and social network inclusion, while coaching with and without school-based teams will result in improved peer engagement and social skills.

Discussion

Previous research has documented barriers to RR implementation at both the individual- (provider) and organization-level (school). Using multi-level implementation strategies such as coaching with school-based teams may address these barriers and support RR implementation in schools. Findings from this study may guide future efforts to scale up tailored implementation strategies for use in public school districts, with the ultimate goal of increasing intervention access and improving student outcomes.

Trial registration

Name of the Registry: clinicaltrials.gov.

Trial Registration: Clinical Trials ID: NCT06559267.

Date of Registration: August 15, 2024. Prospectively registered.
Eco-sustainable chromatographic method for the determination of favipiravir and nitazoxanide for COVID-19: application to human plasma
Authors: Ahmed Amal B. , Abdelrahman Maha M. , Edrees Fadwa H.
Published: January 2025

Coronavirus disease 2019 (COVID-19), an extremely contagious illness, has posed enormous challenges to healthcare systems around the world. Although the evidence on COVID-19 management is growing, antiviral medication is still the first line of treatment. Therefore, it is critical that effective, safe, and tolerable antivirals be available to treat early COVID-19 and stop its progression. Recently, favipiravir (FAV) has received FDA approval as safe and effective antiviral medication for COVID-19 management. Nitazoxanide (NTZ) also possesses antiviral and immunomodulating activities. Moreover, FAV and NTZ in combination are clinically used in COVID-19 treatment with reported safety, synergistic antiviral and immunomodulating effects. Despite the availability of various clinical studies on both FAV and NTZ, no existing analytical application for the simultaneous estimation of FAV and NTZ exists. As a result, the current work goal is to establish a green HPLC method for their analysis and implementation to human plasma. The developed method utilizes isocratic elution with 0.1% aqueous formic acid: ethanol (55:45, v/v) and dantrolene as internal standard. The bioanalytical validation parameters passed the FDA acceptance criteria. NEMI, eco scale, AGREE and ComplexGAPI approaches were used for qualitative and quantitative evaluation of the method’s greenness.
Integrating CT-based radiomics and clinical features to better predict the prognosis of acute pancreatitis
Authors: Chen Hang , Wen Yao , Li Xinya , Li Xia , Su Liping , Wang Xinglan , Wang Fang , Liu Dan
Published: January 2025

Objectives

To develop and validate the performance of CT-based radiomics models for predicting the prognosis of acute pancreatitis.

Methods

All 344 patients (51 ± 15 years, 171 men) in a first episode of acute pancreatitis (AP) were retrospectively enrolled and randomly divided into training (n = 206), validation (n = 69), and test (n = 69) sets with the ratio of 6:2:2. The patients were dichotomized into good and poor prognosis subgroups based on follow-up CT and clinical data. The radiomics features were extracted from contrast-enhanced CT. Logistic regression analysis was applied to analyze clinical-radiological features for developing clinical and radiomics-derived models. The predictive performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).

Results

Eight pancreatic and six peripancreatic radiomics features were identified after reduction and selection. In the training set, the AUCs of clinical, pancreatic, peripancreatic, radiomics, and combined models were 0.859, 0.800, 0.823, 0.852, and 0.899, respectively. In the validation set, the AUCs were 0.848, 0.720, 0.746, 0.773, and 0.877, respectively. The combined model exhibited the highest AUC among radiomics-based models (pancreatic, peripancreatic, and radiomics models) in both the training (0.899) and validation (0.877) sets (all p < 0.05). Further, the AUC of the combined model was 0.735 in the test set. The calibration curve and DCA indicated the combined model had favorable predictive performance.

Conclusions

CT-based radiomics incorporating clinical features was superior to other models in predicting AP prognosis, which may offer additional information for AP patients at higher risk of developing poor prognosis.

Critical relevance statement

Integrating CT radiomics-based analysis of pancreatic and peripancreatic features with clinical risk factors enhances the assessment of AP prognosis, allowing for optimal clinical decision-making in individuals at risk of severe AP.

Key Points

Radiomics analysis provides help to accurately assess acute pancreatitis (AP).

CT radiomics-based models are superior to the clinical model in the prediction of AP prognosis.

A CT radiomics-based nomogram integrated with clinical features allows a more comprehensive assessment of AP prognosis.

Graphical Abstract
The prognostic role of cardiac and inflammatory biomarkers in extubation failure in patients with COVID-19 acute respiratory distress syndrome
Authors: Groenland Carline N. L. , Siemers Adinde H. , Dubois Eric A. , Gommers Diederik , Heunks Leo , Wils Evert-Jan , Baggen Vivan J. M. , Endeman Henrik
Published: January 2025

Background

Extubation failure is associated with an increased morbidity, emphasizing the need to identify factors to further optimize extubation practices. The role of biomarkers in the prediction of extubation failure is currently limited. The aim of this study was to investigate the prognostic value of cardiac (N-terminal pro–B-type natriuretic peptide (NT-proBNP), High-sensitivity Troponin T (Hs-TnT)) and inflammatory biomarkers (Interleukin-6 (IL-6) and Procalcitonin (PCT)) for extubation failure in patients with COVID-19 Acute Respiratory Distress Syndrome (C-ARDS).

Materials and methods

In this single-center retrospective cohort study, patient characteristics and laboratory measurements were extracted from electronic medical records. Patients were eligible for inclusion if they were extubated after mechanical ventilation. The primary endpoint was extubation failure, defined as the need for reintubation or death within the next seven days after extubation, regardless of whether post-extubation respiratory support was used. Uni- and multivariable logistic regression was performed to investigate the association between biomarkers and extubation failure. Biomarkers were log2 transformed.

Results

Of the 297 patients included, 21.5% experienced extubation failure. In univariable analysis, NT-proBNP (OR 1.24, 95% CI 1.06–1.47), Hs-TnT (OR 1.72, 95% CI 1.37–2.19) and PCT (OR 1.38, 95% CI 1.16–1.65) measured on the day of extubation were significantly associated with extubation failure. After multivariable adjustment for clinical variables (age, duration of mechanical ventilation, SOFA score), Hs-TnT was the only biomarker that was independently associated with extubation failure (adjusted OR 1.38, 95% CI 1.02–1.90). Patients with both elevated Hs-TnT (≥ 14 ng/mL) and elevated PCT (≥ 0.25 ng/mL) carried the highest risk of extubation failure (46%), while in patients with normal Hs-TnT and PCT values, only 13% experienced extubation failure.

Conclusions

Hs-TnT, NT-proBNP and PCT measured on the day of extubation are associated with extubation failure in mechanically ventilated patients with C-ARDS. Since Hs-TnT is the only biomarker that is independently associated with extubation failure, Hs-TnT could offer additional objective measures for assessing readiness for extubation. Future studies should focus on an integrative approach of biomarkers combined with relevant clinical factors to predict extubation failure.
MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer
Authors: Sui Xin-Yi , Cao Shuo-Wen , Song Xiao-Qing , Liu Xi-Yu , Chen Chao , Yan Qingya , Wang Zhi-Qing , Zhang Wen-Juan , Ma Lin-Xiaoxi , Jin Xi , Ma Ding , Xiao Yi , Wu Song-Yang , Xu Ying , Shao Zhi-Ming , Fan Lei
Published: January 2025

Background

Although immunotherapy has achieved great progress in advanced triple-negative breast cancer (TNBC), there are still numerous patients who do not benefit from immunotherapy. Therefore, identification of the key molecule that induces immune escape and clarification of its specific mechanism in TNBC are urgently needed.

Methods

In this research, single cell sequencing and bulk sequencing were conducted for biomarker screening. Immunohistochemistry, multiplex immunofluorescence, and orthotopic TNBC tumor model were applied in identifying the key molecule driving immune escape. At the mechanical level, RNA sequencing, in vitro co-culturing system, flow cytometry, Western blotting, ELISA, and real-time qPCR were carried out.

Results

Mortality factor 4 like 2 (MORF4L2) expression is significantly up-regulated among patients who developed anti-PD1 resistance. MORF4L2 enhances anti-PD1 resistance by inducing the chemotaxis of macrophage infiltration and promoting their polarization towards the alternative activation phenotype (M2), thus creating an immunosuppressive microenvironment. Mechanistically, MORF4L2 actes as part of NuA4 histone acetyltransferase (HAT) complex, contributes to to histone 4 lysine 12 acetylation (H4K12Ac) and activates the downstream transcription of macrophage colony-stimulating factor (CSF1). CSF1 is secreted by tumor cells and binds to the macrophage-surface CSF1 receptor (CSF1R), which chemotactically converted and polarized macrophages to the M2 phenotype. Furthermore, we revealed that grainyhead like transcription factor 2 (GRHL2) could promote MORF4L2 transcription by binding to the MORF4L2 enhancer region. Notably, BLZ549, an inhibitor of CSF1R, restored the anti-PD1 sensitivity by blocking the GRHL2/MORF4L2/H4K12Ac/CSF1 axis.

Conclusions

GRHL2/MORF4L2/H4K12Ac/CSF1 axis plays an important role in anti-PD1 resistance. CSF1R inhibitors can reverse GRHL2/MORF4L2-mediated anti-PD1 resistance.
SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis
Authors: Chen Fanghui , Lang Liwei , Yang Jianqiang , Yang Fan , Tang Sijia , Fu Zhenzhen , Saba Nabil F. , Luo Ming , Teng Yong
Published: January 2025

Background

Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods

The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S. Head and neck squamous cell carcinoma (HNSCC) cell lines and orthotopic mouse models were employed for research. Morphological changes were observed using both light microscopy and transmission electron microscopy. Molecular alterations were analyzed through Western blotting and ELISA kits. The tumor secretome was characterized using a combination of biotinylation and LC-MS analysis. Immune cell changes were evaluated by flow cytometry and immunohistochemistry.

Results

Compared to its parental virus, VSV-S not only increases apoptosis by overexpressing SMAC during VSV infection but also triggers elevated levels of PANoptosis (pyroptosis, apoptosis, and necroptosis) in HNSCC cells via activation of caspase-1/gasdermin D (GSDMD) signaling. As a result, VSV-S-induced PANoptosis promotes CD8+ T cell tumor infiltration and enhances their cytotoxic capacity, eventually potentiating T cell-mediated antitumor immunity. Moreover, VSV-S reduces PDL1 levels in HNSCC cells and, in combination with PD1 blockade, produces a more potent antitumor effect than either therapy alone.

Conclusions

Our findings demonstrate that the combination of VSV-S and PD1 blockade offers a synergistic therapeutic strategy for HNSCC, supporting the advancement of VSV-based virotherapy as a promising strategy to improve outcomes for HNSCC patients.
COping with Rheumatic Stressors (CORS) questionnaire: validated German translation and cross-cultural adaptation for patients with axSpA
Authors: Vaupel Kristina , Kiefer David , Ramiro Sofia , Kiltz Uta , van Lankveld Wim , Hammel Ludwig , Baraliakos Xenofon
Published: January 2025

Background

Patients with Rheumatic and Musculoskeletal Diseases, including axial spondyloarthritis (axSpA), may suffer from stressors like pain and functional impairments leading to limitations in their self-perceived health status. The COping with Rheumatic Stressors (CORS) questionnaire was developed to analyze how patients cope with these stressors. The CORS is currently not available in German.

Objective

First, to translate, cross-culturally adapt and to linguistically validate the original Dutch CORS into German. Second, to test the pre-final German translation through cognitive debriefing in patients with axSpA.

Methodology

The original Dutch CORS underwent a multistep cross-cultural adaptation process, as described by Beaton. It was first independently translated into German by bilingual Dutch-German lay and expert translators. Subsequently, it was translated back from the German version into Dutch. Remaining discrepancies were resolved by a scientific committee, resulting in a pre-final German version. This version was then tested through cognitive debriefing by 10 patients with axSpA across a broad spectrum of sociodemographic backgrounds.

Results

Forward and backward translations of the CORS revealed minor discrepancies, mainly based on the degree of formal versus informal language usage, minor semantic errors or unusual syntax, which led to minor modifications in the wording. Reviewed by the scientific committee, the pre-final consensus German version was linguistically validated by cognitive debriefing by 10 patients with axSpA. Cognitive debriefing confirmed and ensured closest linguistic validity for German in Germany and highest equivalence to the Dutch original version.

Conclusion

The German CORS was shown to have high cross-cultural and face validity for the assessment of coping with rheumatic stressors.
Spontaneous orbital meningoencephalocele and temporal encephalocele: An odd cause of proptosis and seizure, a case report and literature review
Authors: El Graini S. , Retal H. , Habib Chorfa S. , Ech-Cherif El Kettani N. , Fikri M. , Jiddane M. , Touarsa F.
Published: January 2025

Meningoencephaloceles (MEC) of the skull base commonly result from head trauma, or congenital malformation, or may arise spontaneously due to increased intracranial pressure, leading to a bony defect and subsequent herniation of brain parenchyma. Spontaneous MEC at orbital and temporal locations are rare, with only a few cases reported in the literature. Brain MRI is typically used for diagnosis, and treatment may be medical or surgical, depending on the size of the bony defect. We present an unusual case of a 69-year-old woman with spontaneous orbital and temporal MEC, resulting in proptosis, strabismus, and seizures secondary to idiopathic intracranial hypertension (IIH). This condition was managed medically, with a favourable outcome. This report aims to describe and analyse the case, reviewing the literature on spontaneous MEC in adult patients at different locations caused by IIH and their management, emphasizing the critical role of imaging in diagnosing this etiology.
Assessment of efficacy and safety of imatinib as an adjunct host-targeted therapy for parasite clearance in chloroquine-resistant malaria: a prospective case control study
Authors: Zubair Ahmed Fazeel , P Shaifulla
Published: January 2025

Overview

Chloroquine-resistant malaria poses a significant treatment challenge, especially in endemic areas. Host-targeted therapies, like tyrosine kinase inhibitors (TKIs) such as imatinib, have shown potential to improve malaria treatment outcomes by disrupting parasite egress from red blood cells. This study investigates the efficacy and safety of imatinib as an adjunct therapy to accelerate fever reduction and parasite clearance in male patients with chloroquine-resistant malaria.

Patients and methods

This open-label, prospective, randomized case–control study was conducted on 60 male patients aged 18–50, diagnosed with chloroquine-resistant malaria at Viswabharathi Medical College, India. Patients were randomized into two groups: a control group receiving standard anti-malarial therapy and a test group receiving standard therapy plus imatinib (400 mg daily for 3 days). Efficacy endpoints included the time to reduce parasite load by half and normalization of body temperature. Safety assessments monitored adverse reactions throughout the treatment period.

Results

The imatinib group demonstrated a significantly faster reduction in fever, with normalization by day 2 compared to day 3 in the control group (p < 0.05). Parasite counts decreased more rapidly in the imatinib group, with mean levels falling to below 1000 parasites/mcl by day 3. Mild adverse effects, primarily headaches and gastrointestinal symptoms, were reported but resolved by day 3 with no severe events directly attributed to imatinib.

Conclusion

Imatinib as an adjunct therapy may enhance the efficacy of standard anti-malarial treatments by accelerating parasite clearance and fever reduction in cases of chloroquine-resistant malaria. These findings support further investigation into TKIs as a complementary approach to existing malaria treatments, particularly in regions facing drug resistance challenges.
Assessing heavy metal contamination in leafy vegetables and associated health risks in Dhaka, Bangladesh
Authors: Hosen Anowar , Jahan Rumana Akther , Simol Hasina Akhter , Huda Muhammad Nurul
Published: January 2025

Leafy vegetables, widely consumed for their nutritional benefits, can pose significant health risks when contaminated with toxic metals, emphasizing the need to monitor and assess their safety. An atomic absorption spectrophotometer (AAS) was used to analyze the metal accumulation in leafy vegetables. The specific minerals analyzed included calcium (Ca), magnesium (Mg), zinc (Zn), manganese (Mn), and iron (Fe). Additionally, heavy metals such as copper (Cu), cadmium (Cd), lead (Pb), chromium (Cr), cobalt (Co), and nickel (Ni) were also examined. Risk factors for the human population were examined, focusing on the transfer of metals from different sources to vegetable samples. These metals were then consumed by humans through the ingestion of leafy vegetables that had accumulated them. The results of this study showed that the average concentrations detected ranged from 68.0 to 1507 mg/kg of Ca, 126.0 to 829.0 mg/kg of Mg, 4.03 to 44.0 mg/kg of Zn, 2.7 to 74.5 mg/kg of Mn, 25.0 to 154.5 mg/kg of Fe, 0.74 to 4.51 mg/kg of Cu, 0.005 to 0.22 mg/kg of Cd, 0.19 to 1.75 mg/kg of Pb, 0.43 to 4.69 mg/kg of Cr, 0.005 to 0.39 mg/kg and 0.25 to 2.21 mg/kg of Ni. The highest mean levels of minerals like Ca, Mg, Zn, Mn and Fe were detected in red amaranth, Garden purslane, Stem amaranth. The study used, estimated daily intakes (EDIs), target hazard quotient (THQ), and cancer risk (CR) assessments to assess the potential health risks of consuming contaminated vegetables. The results showed that the value of THQ was found to be larger than 1 in the cases of Pb and Mn in Stem Amaranth, indicating a significant non-carcinogenic health risk, especially due to high lead exposure exceeding the standard limit by two-fold in all fields. Furthermore, the CR values for Cd, Cr, and Ni indicated a notable carcinogenic risk in multiple cases.
Basal and stimulated inhibin B in pubertal disorders
Authors: Chaudhary Shakun , Walia Rama , Quinton Richard
Published: January 2025

Pubertal disorders in the form of delayed puberty (DP) or precocious puberty (PP) can cause considerable anxiety to both children and parents. Since the clinical and biochemical signatures of self-limiting and permanent conditions overlap considerably, it can be hard to determine whether to offer them reassurance or intervention. Researchers have thus long been searching for a robust test to indicate that the process of endogenous puberty is underway and is likely to proceed to completion. Although existing tests are available, such as basal gonadotropins, gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone, and basal and human chorionic gonadotropin-stimulated testosterone, their diagnostic specificity is inadequate.

Inhibin B, a glycoprotein hormone, is secreted by Sertoli cells in males and small antral follicles in females. The entry into puberty is characterized by a rise in inhibin B levels in both genders. For the past two decades, researchers have been studying the role of inhibin B in the differential diagnosis of DP as well as PP. Initial studies showed promising results for using inhibin B to distinguish between constitutional (or self-limited) DP (SLDP) and congenital hypogonadotropic-hypogonadism (CHH). However, diverse population studies have revealed varying cut-offs, limiting the use of basal inhibin B(basal-iB) in routine clinical practice. Recently, the concept of stimulated inhibin B has been introduced, using either follicle-stimulating hormone (FSH) or GnRH-analogs. Both FSH- and GnRH-analog-stimulated inhibin B concentration were found to be more reliable than basal levels in the investigation of pubertal disorders. This review examines the current status of basal-iB in the differential diagnosis of delayed and precocious puberty, addressing its main advantages and limitations, and shedding light on the role of stimulated inhibin B concentrations.
Treatment of Hyperthyroidism in Graves' Disease Complicated by Thyroid Eye Disease
Authors: Bartalena Luigi , Smith Terry J
Published: January 2025

Thyroid eye disease (TED) is the most consequential extrathyroidal manifestation or complication of Graves' disease (GD). Treatment of hyperthyroidism in GD complicated by TED is challenging. Antithyroid drugs (ATDs) and thyroidectomy do not change the natural course of TED, while radioactive iodine (RAI) is associated with a small but well-documented risk of TED de novo occurrence or its progression/worsening. In the presence of mild TED, any treatment for hyperthyroidism can be used, but should RAI treatment be selected, steroid prophylaxis (short course of low-dose prednisone) is strongly recommended if TED is of recent onset and/or risk factors for progression exist. In moderate to severe and active TED, ATDs are the preferred treatment, but thyroidectomy is a valid option. RAI ablation is generally avoided; it might be used when the clinical situation calls for it, but with extreme caution, if an aggressive treatment for TED with high-dose glucocorticoids (with or without orbital radiotherapy) is administered concomitantly. In moderate to severe and inactive TED, all 3 treatments for hyperthyroidism are acceptable, and steroid prophylaxis in RAI-treated patients should be given when risk factors for TED progression are identified. Management of sight-threatening TED represents the absolute priority, and hyperthyroidism should be controlled with ATDs until TED has been controlled.

Search Strategies

Current guidelines, original articles, clinical trials, systematic reviews, and meta-analyses up to June 2024 were searched using the following terms: “Graves' disease,” “management of Graves' disease,” “antithyroid drugs,” “radioactive iodine,” “thyroidectomy,” “thyroid eye disease,” “Graves' orbitopathy or ophthalmopathy.”
Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia
Authors: Ali Dalal S , Mirza Reza D , Hussein Salma , Alsarraf Farah , Alexander R Todd , Abu Alrob Hajar , Appelman-Dijkstra Natasha M , Biosse-Duplan Martin , Brandi Maria Luisa , Carpenter Thomas O , Chaussain Catherine , Dandurand Karel , Filler Guido , Florenzano Pablo , Fukumoto Seiji , Grasemann Corinna , Imel Erik A , Jan de Beur Suzanne M , Morgante Emmett , Ward Leanne M , Khan Aliya A , Guyatt Gordon
Published: January 2025

Objective

To examine the evidence addressing the management of X-linked hypophosphatemia (XLH) in children to inform treatment recommendations.

Methods

We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included randomized controlled trials (RCTs) and observational studies of individuals younger than 18 years with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to either no treatment or conventional therapy (phosphate and active vitamin D) or evaluating conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty.

Results

We screened 4114 records and assessed 254 full texts. One RCT and one post hoc study proved eligible when comparing burosumab to conventional therapy or no treatment. The open-label RCT was at high RoB, with certainty of evidence ranging from moderate to very low. Burosumab, compared to conventional therapy, probably prevents lower limb deformity and improves physical health quality of life (QoL) (moderate certainty). Burosumab may increase height and enhance the burden of symptoms related to chronic hypophosphatemia (low certainty). Burosumab probably increases treatment-emergent adverse events (moderate certainty) and may increase dental abscesses (low certainty). One observational study assessing conventional therapy vs no treatment was at high RoB, providing very low certainty evidence regarding the impact of conventional therapy on final height.

Conclusion

Our review indicates that burosumab likely provides benefits to children by preventing lower limb deformity and improving physical health QoL while potentially increasing height. However, burosumab may also increase adverse events. Our review found limited evidence regarding the impact of conventional therapy compared to no treatment on final height. Further research is required to understand the long-term effect of medical therapy in children.
Co-Occurrence of Sotos Syndrome and Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome in 2 Patients
Authors: Mustafa Manahil , Mitscher Mary K , Johnson Nancy B , Fuqua John S
Published: January 2025

Sotos syndrome is an autosomal dominant condition caused by a pathogenic variant of NSD1 and characterized by a distinctive facial appearance, learning disability, and overgrowth. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by agenesis or aplasia of the uterus and upper part of the vagina in females with a normal female karyotype. The coexistence of the 2 syndromes has been reported only twice to date. We describe 2 girls with Sotos syndrome who presented with primary amenorrhea. The patient in case 1 had central precocious puberty diagnosed at age 6.5 years, which was appropriately managed for 2 years. The patient in case 2 had congenital hypothyroidism due to thyroid aplasia, treated with levothyroxine. Investigations in both girls revealed normal gonadotropin and estradiol levels. Pelvic ultrasound and magnetic resonance imaging showed absence of the uterus and the presence of normal ovaries. Based on these findings, both patients were diagnosed with müllerian agenesis/MRKH. The presence of Sotos and MRKH syndromes in these 2 patients, along with the 2 previously documented cases, might be coincidental. However, with 4 reported cases, the possibility exists for a rare link between Sotos syndrome and MRKH. Additionally, the psychosocial effect of infertility should not be underestimated.
Placas fotovoltaicas: um futuro brilhante com um pós-vida sombrio
Authors: Alves Ana Paula Antão , Branchini Luciana Oliveira e Rocha
Published: January 2025

A SolTec, empresa brasileira de produção de painéis fotovoltaicos (FV), apresenta um dilema crucial para a indústria solar brasileira e global: como garantir a sustentabilidade de uma tecnologia limpa como a energia solar, considerando o impacto ambiental do descarte de seus componentes no final de sua vida útil? Os alunos assumem o papel de Luana Santos, CEO da SolTec, que precisa encontrar uma solução para o crescente volume de resíduos, com descarte inadequado e pressão dos stakeholders por soluções sustentáveis. O caso de ensino explora as opções e desafios que Luana enfrenta, convidando os alunos a propor soluções inovadoras e estimulando a reflexão sobre o futuro das organizações em um mundo que caminha para uma economia circular e sustentável.
A Comparative Analysis of Parent-Centered versus Parent-Adolescent Dyad Interventions to Enhance HPV vaccination Uptake in Children and Adolescents: Protocol for Systematic Review and meta-analysis
Authors: Bhengu P , Ndwandwe D , Kuodi P , Tamuzi JL , Wiysonge CS , Mazingisa AV , Mavundza EJ , Cooper S , Katoto PDMC , Shey M
Published: January 2025

Background Human papillomavirus (HPV) vaccination among children and adolescents is crucial for the prevention of HPV-related diseases later in life. However, HPV vaccination uptake remains suboptimal in this population. This protocol outlines a comprehensive review that aims to evaluate the effectiveness of interventions targeting parents and parent-adolescent dyads in improving HPV vaccination uptake among children and adolescents aged 9-18 years. Objective The objective of this study is to assess the impact of parent-directed and parent-adolescent dyad interventions on HPV vaccination uptake in children and adolescents aged 9-18 years. Specific objectives include reviewing existing literature on parent-oriented and parent-adolescent dyad interventions, assessing vaccination uptake, identifying influencing factors, and providing evidence-based recommendations for intervention development and implementation. Methods A systematic review will be conducted, encompassing literature published up to the present day. Various databases will be searched for relevant studies on parent-focused and parent-adolescent dyad interventions aimed at improving HPV vaccination uptake. Data extraction and analysis will be performed to assess the proportion of children and adolescents receiving HPV vaccination following interventions, factors influencing vaccination uptake, and completion rates of the recommended vaccine series. Results The review findings will be analyzed using appropriate statistical methods, including meta-analysis to estimate the overall effect size of interventions. Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of the results. Conclusion This protocol outlines a comprehensive review that will contribute to the current understanding of the effectiveness of parent-oriented and parent-adolescent dyad interventions in improving HPV vaccination uptake among children and adolescents. The findings will inform the development and implementation of targeted interventions to address barriers and improve vaccination coverage, ultimately reducing the burden of HPV-related diseases.
Research protocol - Evaluating data quality in the Netherlands Perinatal Registry (Perined): A data comparison study using hospital records from the IUGR Risk Selection (IRIS) study
Authors: Plomp Hilde , Verhoeven Corine , Peters Lilian , van Dijk Aimée , Onland Wes , de Jonge Ank , Henrichs Jens
Published: January 2025

Background The quality of registry based studies depends largely on the data accuracy of the registries. The Dutch Perinatal Registry (Perined) is a nationwide database comprising perinatal data digitally provided by different healthcare providers. Perined data are used for comparing outcomes across regions and healthcare institutions as well as for quality analyses and research purposes. However, little is known about the data quality of the Perined database. Therefore, this research protocol depicts our proposed study assessing the quality of Perined data compared to hospital records and case report forms (CRFs) that were part of the IUGR Risk Selection (IRIS) study. Methods In the planned comparison study data from Perined and the IRIS Study will be used. The IRIS study was a large cluster-randomized trial investigating the effectiveness of routine third trimester ultrasonography in reducing severe adverse perinatal outcomes among Dutch low-risk pregnant women. A subsample of the IRIS study of neonates being at risk of severe adverse perinatal outcomes and their mothers will be used. Baseline demographic data were collected by midwives from participating women at inclusion (around 22 weeks’ gestation) using CRFs, and in-depth neonatal and maternal clinical data were retrieved from hospital records by trained research assistants. These latter IRIS study data were linked and compared to Perined data. Completeness of Perined data will be calculated for every variable. The reliability will be assessed as the percent of agreement between Perined and hospital record data or the CRF-based data. Additionally, intra-class correlation coefficients will be calculated for continuous variables, and Kappa and ‘Prevalence-and-Bias-Adjusted Kappa’ will be calculated for categorical variables. Discussion The results of the planned comparison study will provide users of Perined data insight in its data quality. This will serve as an example of the accuracy of registry based data used in maternal and neonatal care research.
Morphological and Molecular Characterization of Trichoderma Isolates from Vegetable Crop Rhizospheres in Nepal
Authors: Jaiswal Puja , Khadka Ram B. , Hussain Bhat Aashaq , Baidya Suraj , Keshari Arvind Kumar
Published: January 2025

Background Trichoderma spp. hold significant potential as biocontrol agents in agriculture due to their antagonistic properties against plant pathogens. The study aimed to characterize and identify Trichoderma isolates from rhizospheric regions of vegetable crops. Methods In this study, Trichoderma isolates were collected from rhizospheric soil samples of vegetable crops from different ecological zones and were selected for comprehensive morphological and molecular characterization. The isolates were visually assessed for colony color, growth pattern, aerial mycelium presence, phialide and conidial morphology, and chlamydospore presence. Molecular analysis was employed based on ITS and tef-1α sequences. Diversity indices were also computed for different ecological zones. Results The morphological characteristics and phylogenetic trees for both regions provided a clear species resolution, with four main clades: Harzianum, Viride, Brevicompactum and Longibrachiatum with 12 species T. harzinaum, T. afroharzianum, T. lentiforme, T. inhamatum, T. camerunense, T. azevedoi, T. atroviride, T. asperellum, T. asperelloides, T. koningii, T. longibrachiatum and T. brevicompactum and nine species as a new country record. Diversity indices indicated that high mountain regions displayed the highest species diversity and evenness (H = 1.724 [0.28], J = 0.84, D = 0.28), followed by hilly regions (H = 1.563 [0.28], J = 0.72, D = 0.28). Plains, on the other hand, exhibited lower species diversity (H = 1.515, J = 0.66, D = 0.33). The calculated species abundance values showed that plains (E = 2.11), mid-hills (E = 1.95), and high mountains (E = 1.99) each had their unique diversity profiles. Notably, T. afroharzianum and T. asperellum were predominant. Conclusions Overall, the study unveiled a rich diversity of Trichoderma species in different agricultural zones of Nepal. These findings shed light on the ecological distribution and diversity of Trichoderma spp., which could have significant implications for sustainable agriculture and biological control strategies.
Primary and Secondary Prevention of Obesity
Authors: Kiełczewska Aleksandra , Szcześniak Grzegorz , Kiełczewska Anna
Published: January 2025

Introduction and purpose: Obesity is a persistent and recurring chronic condition marked by an excessive accumulation of body fat, which can deteriorate health, heighten the risk of complications, and shorten life expectancy.This review provides a comprehensive overview of the primary and secondary prevention of obesity, with a focus on interventions and strategies.
Material and methods: An extensive examination of articles published in scientific journals was carried out through online research  platforms PubMed and Google Scholar.  We searched articles by entering keywords in appropriate configuration: “primary prevention of obesity”, “secondary prevention of obesity”, “obesity”.
Description of the state of knowledge: According to published data, the growing problem of obesity translates into negative consequences in the form of the development of numerous complications associated with it and a shortening of the life expectancy of patients. Primary prevention of obesity includes health policy and health care that aim to prevent the development of obesity. Secondary prevention focuses on detecting and treating obesity at an early stage to prevent the development of complications.
Summary: Implementing comprehensive primary prevention strategies across the population could substantially decrease the occurrence of numerous chronic conditions associated with overweight and obesity, yet effective large-scale programs to achieve this are currently lacking.
Berghain, Techno and the Body Factory
Authors: Robin Guillaume
Published: January 2025

This research explores the sociological dimensions of Berghain—the iconic Berlin techno club—by focusing on its regular attendees and their shared experience of secrecy. The fieldwork-based study draws parallels between Berghain and ancient Bacchanalian rites, both spaces where social norms are suspended, allowing for a collective transformation of bodies and identities. It emphasizes the club’s “code of silence” as a vital element of the communal experience, creating a space where anonymity and discretion are key. Methodologically, Robin employs ethnographic methods, by combining qualitative interviews and participant observation sessions, immersing himself in the Berghain scene to understand how this secrecy fosters a sense of belonging among regulars and releases the body. This research also explores how the COVID 19 pandemic has reshaped the club's sociological contours, including shifts in the audience and the reinvention of the space. Overall, this study addresses how secrecy, rituals, and social dynamics at Berghain shape its audience's collective identity.
Nurse Staffing Under Absenteeism: A Distributionally Robust Optimization Approach
Authors: Ryu Minseok , Jiang Ruiwei
Published: January 2025

Problem definition: We study a nurse staffing problem under random nurse demand and absenteeism. Although the demand uncertainty is exogenous, the absenteeism uncertainty is decision-dependent, that is, the number of nurses who show up for work partially depends on the nurse staffing level. For quality of care, hospitals develop float pools of hospital units and train nurses to be able to work in multiple units (termed cross-training) in response to potential nurse shortages. Methodology/results: We study a distributionally robust nurse staffing (DRNS) model that considers both exogenous and decision-dependent uncertainties. We derive a separation algorithm to solve this model under a general structure of float pools. In addition, we identify several pool structures that often arise in practice and recast the corresponding DRNS model as a mixed-integer linear program, which facilitates off-the-shelf commercial solvers. Managerial implications: Through the numerical case studies, based on the data of a collaborating hospital, we found that modeling decision-dependent absenteeism improves the out-of-sample performance of staffing decisions, and such improvement is positively correlated with the value of flexibility arising from fully utilizing float pools.

Funding: R. Jiang was supported in part by the National Science Foundation [Grant ECCS-1845980].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0398 .
DOES A THEORY-OF-VALUE ADD VALUE? EVIDENCE FROM A RANDOMIZED CONTROL TRIAL WITH TANZANIAN ENTREPRENEURS
Authors: Agarwal Rajshree , Bacco Francesca , Camuffo Arnaldo , Coali Andrea , Gambardella Alfonso , Msangi Haji , Sonka Steven , Temu Anna , Waized Betty , Wormald Audra
Published: January 2025

Entrepreneurs making decisions under uncertainty are encouraged to evaluate their initial ideas through hypothesis testing, but entrepreneurial approaches vary in their emphasis on ex-ante theory development prior to collecting evidence. In this paper, we examine whether and how entrepreneurs benefit from adopting an evidence-based approach or a theory-and-evidence-based approach to decision-making. We conducted a field experiment with Tanzanian agribusiness entrepreneurs by randomly assigning entrepreneurs to two different training conditions. We find that entrepreneurs in the theory-and-evidence-based condition have higher economic performance during the observation period following the intervention. We conjecture this result stems from differences in the types of changes enacted: entrepreneurs in the theory-and-evidence-based training make more coordinated changes that encompass both core and operational elements of their business models.
Studi literatur tentang pembelajaran matematika berbasis teknologi dengan pendekatan kearifan lokal
Authors: Usman Usman
Published: January 2025

Penelitian ini merupakan studi literatur yang bertujuan untuk mengeksplorasi tantangan dan peluang dalam penerapan pembelajaran matematika berbasis teknologi dengan pendekatan kearifan lokal di era digital. Melalui telaah berbagai sumber literatur, penelitian ini mengidentifikasi tantangan utama seperti keterbatasan infrastruktur teknologi, kurangnya pelatihan guru dalam penggunaan teknologi, serta kesulitan dalam menyelaraskan konten matematika dengan elemen kearifan lokal. Selain itu, kesenjangan akses teknologi antara daerah perkotaan dan pedesaan menjadi hambatan dalam implementasi yang merata. Di sisi lain, peluang yang muncul dari integrasi teknologi dan kearifan lokal sangat potensial, antara lain pengembangan media pembelajaran yang lebih interaktif, personalisasi pembelajaran sesuai konteks budaya, serta peningkatan motivasi siswa dalam belajar matematika. Teknologi seperti aplikasi mobile, platform pembelajaran daring, dan realitas tertambah yang digunakan untuk mengaitkan konsep matematika dengan nilai-nilai budaya lokal, menjadikannya lebih relevan dan kontekstual bagi siswa. Hasil penelitian menyimpulkan bahwa penerapan pembelajaran matematika berbasis teknologi dengan pendekatan kearifan lokal tidak hanya meningkatkan kualitas pendidikan, tetapi juga memperkuat identitas budaya siswa. Namun, kesuksesannya memerlukan dukungan kebijakan, pelatihan guru, dan pengembangan infrastruktur teknologi yang memadai.
Telemedicine: how to achieve interoperability without compromising data security
Authors: Sahu Kavita , Kumar Rajeev
Published: January 2025

Telemedicine has become a critical component of modern healthcare by improving the accessibility and efficiency of patient services. However, ensuring the security of telemedicine platforms is a growing concern, especially when it comes to interoperability and the exchange of data between platforms.