bluuebunny/crossref_metadata_2025_split huggingface dataset:
MFNG is an independent prognostic marker for osteosarcoma
Authors: Gao Yi , Luo Lili , Qu Yuxing , Zhou Qi 
Published: July 2023

Abstract
Background
Osteosarcoma (OS) has been the most common malignancy of the bone in children and adolescents, and the unsatisfactory prognosis of OS sufferers has long been a hard nut. Here, we delved into the markers with a prognostic value for predicting the prognosis of OS patients.

Methods
The messenger RNA (mRNA) sequencing data and clinical data of OS were retrieved from a Gene Expression Omnibus (GEO) dataset (GSE39058). Next, prognosis-related genes (PRGs) were filtered with the aid of Kaplan–Meier (K-M) curves and Cox regression analysis (CRA). Later, Gene Ontology (GO) biological process analysis was used in verifying the function of different genes. CCK-8 and cell apoptosis assay were performed to evaluate the function of MFNG in U2OS cells.

Results
Among the obtained genes, Manic Fringe (MFNG) had the closest relevance to prognosis and clinical traits, thus becoming the research object herein. In light of the expression level of MFNG, patients fell into high- and low-MFNG groups. Patients with elevated MFNG expression had a worse prognosis, according to the survival analysis. It was unveiled by the univariate and multivariate analyses that MFNG expression was an independent adverse prognostic factor for disease-free survival in OS patients (p = 0.006). Meanwhile, MFNG expression was linked to gender and tumor recurrence, and it was higher in patients with OS recurrence. Moreover, overexpression of MFNG promoted the cell proliferation and inhibited the cell apoptosis of U2OS cells.

Conclusions
The expression level of MFNG negatively correlated with OS progression, and as an independent adverse prognostic factor for disease-free survival in OS patients. Moreover, MFNG regulated the cell proliferation and apoptosis of OS cells.
Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy
Authors: Zheng Xiaogang , Jin Xiaodong , Ye Fei , Liu Xiongxiong , Yu Boyi , Li Zheng , Zhao Ting , Chen Weiqiang , Liu Xinguo , Di Cuixia , Li Qiang 
Published: July 2023

Abstract
Background
Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years.

Methods
We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment.

Result and conclusion
Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.
Darier’s disease exhibits a unique cutaneous microbial dysbiosis associated with inflammation and body malodour
Authors: Amar Yacine , Rogner Danielle , Silva Rafaela L. , Foesel Bärbel U. , Ud-Dean Minhaz , Lagkouvardos Ilias , Steimle-Grauer Susanne A. , Niedermeier Sebastian , Kublik Susanne , Jargosch Manja , Heinig Matthias , Thomas Jenny , Eyerich Stefanie , Wikström Jakob D. , Schloter Michael , Eyerich Kilian , Biedermann Tilo , Köberle Martin 
Published: July 2023

Abstract
Background
Darier’s disease (DD) is a genodermatosis caused by mutations of the ATP2A2 gene leading to disrupted keratinocyte adhesion. Recurrent episodes of skin inflammation and infections with a typical malodour in DD indicate a role for microbial dysbiosis. Here, for the first time, we investigated the DD skin microbiome using a metabarcoding approach of 115 skin swabs from 14 patients and 14 healthy volunteers. Furthermore, we analyzed its changes in the context of DD malodour and the cutaneous DD transcriptome.

Results
We identified a disease-specific cutaneous microbiome with a loss of microbial diversity and of potentially beneficial commensals. Expansion of inflammation-associated microbes such as Staphylococcus aureus and Staphylococcus warneri strongly correlated with disease severity. DD dysbiosis was further characterized by abundant species belonging to Corynebacteria, Staphylococci and Streptococci groups displaying strong associations with malodour intensity. Transcriptome analyses showed marked upregulation of epidermal repair, inflammatory and immune defence pathways reflecting epithelial and immune response mechanisms to DD dysbiotic microbiome. In contrast, barrier genes including claudin-4 and cadherin-4 were downregulated.

Conclusions
These findings allow a better understanding of Darier exacerbations, highlighting the role of cutaneous dysbiosis in DD inflammation and associated malodour. Our data also suggest potential biomarkers and targets of intervention for DD.
Upper limb practice with a dynamic hand orthosis to improve arm and hand function in people after stroke: a feasibility study
Authors: Wong Yih , Ada Louise , Månum Grethe , Langhammer Birgitta 
Published: July 2023

Abstract
Background
Dynamic hand orthosis may help upper limb recovery by keeping the wrist and hand in an optimal position while executing a grasp. Our aim was to investigate the feasibility of combining a dynamic hand orthosis with task-oriented upper limb practice after stroke.

Method
Fifteen adult stroke survivors were recruited in a single-group, pre-post intervention study. They received 12 weeks of task-oriented upper limb training with a dynamic hand orthosis with 3 weeks supervised at a community rehabilitation unit followed by 9 weeks unsupervised at home. Feasibility was determined by recruitment (proportion of eligible/enrolled and enrolled/retained participants), intervention (adherence, acceptability, and safety) and measurement (time taken to collect outcomes and proportion of participants where all measures were collected). Clinical outcomes were measured at baseline (Week 0), end of Week 3 and Week 12.

Results
Fifteen (46%) of eligible volunteers were enrolled in the study. Eight (53%) of those enrolled completed the 12-week intervention. Eighty eight percent were satisfied or very satisfied with the dynamic hand orthosis. Clinical measures were collected for all participants at baseline and in all those who completed the intervention but often took over one hour to complete. At 12 weeks, participants had improved by 7 points out of 57 (95% CI 2 to 13) on the ARAT and by 8 points out of 66 (95% CI 0 to 15) on the FMA-UE.

Conclusion
The intervention appears to be feasible in terms of acceptability and safety, while recruitment and measurement need further consideration. The magnitude of the clinical outcomes suggests that the intervention has a potential to improve both upper limb activity and impairment, and this study provides useful information for the design of a pilot randomized trial.

Trial registration
ClinicalTrials.gov Identifier: NCT03396939.
SOP: acute hyperkinetic movement disorders
Authors: Sauerbier Anna , Gronostay Alexandra , Dafsari Haidar S. 
Published: July 2023

Abstract
Introduction
Movement disorders emergencies describe acute-onset neurological conditions in which a delay of recognition and treatment may cause severe morbidity and mortality of patients. Hyperkinetic movement disorders include tremor, chorea/ballism, dystonia, myoclonus, and tics. Here we present a standard operating procedure (SOP) for the diagnostic work-up and different treatment options depending on the phenomenology as well as the aetiology of underlying diseases.

Comments
The recognition of the phenomenology is essential for the symptomatic therapy of the acute movement disorder and forms the basis for the choice of ancillary investigations to confirm the suspected underlying causes. Furthermore, we summarise diagnostic techniques, including blood and cerebrospinal fluid tests and neuroimaging, which provide rapid results and are useful for the indication of causal treatments of specific acute movement disorders.

Conclusions
Despite their acute nature, most of these conditions can result in good clinical outcomes, if recognised early.
An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients
Authors: Thomford Nicholas Ekow , Adu Faustina , Gavor-Kwashi Cyril , Nyarko Samuel Badu , Nsiah Paul , Ephraim Richard Dadzie , Adjei George , Anyanful Akwasi 
Published: July 2023

Abstract
Background
Organic anion transporters and efflux transporters are involved in the metabolism of drugs such as tenofovir disoproxil fumarate (TDF). Given the important role of organic anions and efflux transporters in drug disposition, genetic variations lead to interindividual differences in drug response. Variations in the SLC and ABC transporters have been associated with drug-induced renal dysfunction. Looking at the prevalence of HBV infection in our population and the use of drugs such as TDF in managing this condition, this study aimed to undertake an exploratory analysis of genetic variation in renal transporters SLC22A6, SLC22A8, ABCC10 and ABCC4 in a Ghanaian HBV infected cohort.

Methods
We genotyped 160 HBV infected patients for SNPs in SLC22A6 (rs12293966, rs4149170, rs6591722, rs955434), SLC22A8 (rs11568487), ABCC10 (rs700008, rs831311) and ABCC4 (rs9282570) genes. Clinicodemographic data was taken, and glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Genotyping was undertaken using Iplex gold SNP genotyping protocol on the Agena MassARRAY® system. Statistical analysis was undertaken using packages in Stata SE (v17) and GraphPad prism. Hardy–Weinberg equilibrium, haplotype inference, and linkage disequilibrium (LD) were evaluated using web-based tools LDlink and Shesis.

Results
The average eGFR was 79.78 ± 33.08 mL/min/1.73 m2 with 31% classified as stage 1 with normal or high GFR (eGFR > 90 mL/min/1.73 m2) and 45% with stage 2 CKD (> 60–89.99 mL/min/1.73 m2). All variants were in HWE except rs4149170, rs9282570 and rs700008 where p < 0.05. Strong LD was observed in the variants rs6591722, rs4149170, rs12293966, rs955434 and rs11568487. There was significant association between rs12293966 and eGFR stage under crude dominant inheritance model (OR 0.27, 95% CI 0.08–0.81; p = 0.019). Under crude model (OR 0.21, 95% CI 0.07–0.66; p = 0.008), adjusted model 1 (OR 76, 95% CI 0.39–7.89; p = 0.014) and adjusted model 2 (OR 0.30, 95% CI 0.12–0.78; p = 0.013) there was significant association observed between rs12293966 and eGFR stage in a codominant inheritance.

Conclusion
The associations observed in this study point to the need for further evaluation with the population of HBV patients on TDF treatment in addition to other factors that would lead to unfavorable outcomes. This exploratory finding may require confirmation in a larger cohort with proper phenotyping to investigate the exact pharmacogenetic mechanisms.
Mapping circular economy principles and servitisation approach in business model canvas: an integrated literature review
Authors: Atif Sehrish 
Published: July 2023

AbstractIt is a common perception that circular economy (CE) principles positively influence the servitisation strategy. The firms improve their productivity and resource/energy efficiency by engineering functional efficacy in a sustainable product. However, the managerial practices that support this distinctive business model (BM) are relatively sparse despite their liaisons. Therefore, this paper is focused on addressing this gap by investigating the managerial practices that firms can implement to explore the downstream opportunities of CE and servitisation BM. This paper uses a systematic literature review (SLR) approach to frame a theoretical model. The findings were improved by cross-validation using a text mining technique, demonstrating how organisations may co-create and extract value through CE and servitisation to develop a flexible management system. This study used the business model canvas antecedents to map a set of managerial practices to understand the mythography of the servitisation approach with CE principles. The findings show that identifying key stakeholders assists a firm in selecting an appropriate strategy based on sustainable value propositions that include cost structure and revenue streams to close the resource loop. Managerial commitment is critical in achieving the maximum economic, environmental, and societal potential. A few research agendas with distinct research orientations are proposed to mitigate the significant research gaps in CE and servitisation literature. This study provides managers and practitioners with some intriguing insights as it emphasises the need to select a suitable strategy to utilise a firm's resources successfully.
Lithium Monotherapy in Graves Thyrotoxicosis
Authors: Larkworthy James , Kirresh Omar , Chakera Ali , Ahmed Fahad 
Published: July 2023

Abstract
Lithium is not commonly used to treat thyrotoxicosis, and there are few reports in the literature of its use as initial therapy in thyrotoxicosis. We describe the case of a patient with Graves thyrotoxicosis and ophthalmopathy, on a background of autoimmune neutropenia, treated successfully with relatively long-term lithium monotherapy. Lithium was used at a lower dose and longer duration than previously reported on, to good effect. We demonstrate that lithium is an important and useful option for those who are unable to tolerate thionamide therapy.
The Organic Monocrop
Authors: Kumpf Desirée 
Published: July 2023

AbstractUnder the banner of green growth, a number of theories currently promote new models that seek to decouple economic growth from excessive resource use and its adverse ecological impacts. But how exactly can one generate profit without disturbing ecologies? Drawing on ethnographic data from Indian tea plantations that are in the process of being converted to organic agriculture, this article examines specific attempts to alter the intersection of vegetal and financial growth. As a cultivation system, plantations intensify the manipulation of plant growth for monetary ends; they seek to mass produce and standardize valuable vegetal materials and radically simplify the ecologies that surround these monocrops. Taking a multispecies perspective, this article traces how green growth experiments seek to change the forms, rhythms, and ecological alliances that characterize the tea plant’s growth. The article argues that, on organic tea plantations, green growth aspires to harness the unruly aspects of nonhuman life to make monocultures more productive. In the process, the nonscalable impulses of vegetal growth, unpredictable interactions with wildlife, and even the potentially harmful metabolisms of insects and fungi become integral parts of plantation cultivation—though not always successfully. The article widens our understanding of how green production methods are envisioned not as alternatives to but rather as support for industrial cultivation systems.
Snake Oil and Gaslight
Authors: Staub Michael E. 
Published: July 2023

Abstract
This article seeks to sidestep the dilemma of restricted access to oil company archives through a close examination of a heretofore underutilized source base: the fossil fuel industry’s own trade journals and magazines. These oil and gas industry trade publications have served to envelop their readership in what we would now call an information bubble. Still, it is important to highlight the contradictory tactics that trade industry publications effectively test-marketed in the 1960s and 1970s to nullify a perception of petroleum as hazardous to public health and the natural environment. Most paradoxical was how trade publications reinvented their industry both as not a problem for the natural environment and as the solution to all and any future problems faced by that environment. Unlike any other currently available source base, Big Oil’s trade publications offer insights into the timing and triggering motivations of the industry’s shift to self-representation as stewards of nature, as well as the rapidity and multidimensional comprehensiveness of the industry’s mobilization to develop counternarratives to potential critics. And not least of all, these publications reveal the fantastical lengths to which Big Oil was willing to go in its efforts to preemptively block the research and development of electric vehicles, principally by diverting to the imaginary prospect of a gasoline-powered but nonetheless “smogless” car. This history represents an early and previously unexplored chapter in the evolution of what we have come to recognize as corporate “greenwashing.”
Clinical evaluation of atlas-based auto-segmentation in breast and nodal radiotherapy
Authors: Welgemoed Camarie , Spezi Emiliano , Riddle Pippa , Gooding Mark J , Gujral Dorothy , McLauchlan Ruth , Aboagye Eric O 
Published: July 2023

Objectives:
Accurate contouring of anatomical structures allows for high-precision radiotherapy planning, targeting the dose at treatment volumes and avoiding organs at risk. Manual contouring is time-consuming with significant user variability, whereas auto-segmentation (AS) has proven efficiency benefits but requires editing before treatment planning. This study investigated whether atlas-based AS (ABAS) accuracy improves with template atlas group size and character-specific atlas and test case selection.

Methods and materials:
One clinician retrospectively contoured the breast, nodes, lung, heart, and brachial plexus on 100 CT scans, adhering to peer-reviewed guidelines. Atlases were clustered in group sizes, treatment positions, chest wall separations, and ASs created with Mirada software. The similarity of ASs compared to reference contours was described by the Jaccard similarity coefficient (JSC) and centroid distance variance (CDV).

Results:
Across group sizes, for all structures combined, the mean JSC was 0.6 (SD 0.3, p = .999). Across atlas-specific groups, 0.6 (SD 0.3, p = 1.000). The correlation between JSC and structure volume was weak in both scenarios (adjusted R 2−0.007 and 0.185).
Mean CDV was similar across groups but varied up to 1.2 cm for specific structures.

Conclusions:
Character-specific atlas groups and test case selection did not improve accuracy outcomes. High-quality ASs were obtained from groups containing as few as ten atlases, subsequently simplifying the application of ABAS. CDV measures indicating auto-segmentation variations on the x, y, and z axes can be utilised to decide on the clinical relevance of variations and reduce AS editing.

Advances in knowledge:
High-quality ABASs can be obtained from as few as ten template atlases.
Atlas and test case selection do not improve AS accuracy.
Unlike well-known quantitative similarity indices, volume displacement metrics provide information on the location of segmentation variations, helping assessment of the clinical relevance of variations and reducing clinician editing. Volume displacement metrics combined with the qualitative measure of clinician assessment could reduce user variability.
Cumulative radiation exposure from radiological imaging in patients with Hodgkin and diffuse large b-cell lymphoma not submitted to radiotherapy
Authors: Brambilla Marco , Matheoud Roberta , Margiotta-Casaluci Gloria , Cannillo Barbara , D'Alessio Andrea , Siciliano Chiara , Carriero Alessandro , Gaidano Gianluca 
Published: July 2023

Objective:
To assess the cumulated exposure to radiation due to imaging in Hodgkin (HL) and diffuse large B-cell (DLBCL) lymphoma patients who were not submitted to radiotherapy.

Methods:
The study population included 51 and 83 adult patients with HL and DLBCL, with a follow-up duration &gt;1 year. The cumulated exposure was expressed using patient-specific data as cumulated effective dose (CED).

Results:
Fifty-one HL patients (median age 47 years) were followed for a median of 3.5 years. The median total CED per subject was 104 mSv. CT and PET/CT examinations accounted for 75 and 25% of the total CED, respectively. 26 patients (49%) had a total CED ≥ 100 mSv and the maximum CED was 302 mSv.
Eighty-three DLBCL patients (median age 66 years) were followed for a median of 3.7 years. The median total CED per subject over the study period was 134 mSv. CT and PET/CT for 86% and 13% of the total CED, respectively. 56 patients (67%) had a total CED ≥100 mSv. The maximum CED was 557 mSv.

Conclusion:
Our study demonstrated the large number of imaging procedures performed for patients with lymphoma. Overall, 61% of the patients accrued a CED ≥ 100 mSv. Imaging policies were only in a partial agreement with current international guidelines.

Advances in knowledge:
The cumulated exposure radiation exposure may be of concern in HL patients and the contribution of CT procedures to the total CED is significant. The standardisation of clinical guidelines for managing patients with lymphoma is warranted.
Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects
Authors: Naseer Hammael , Rasid Amir , Majeed Asifa , Ali Baig Zunaira 
Published: July 2023

Objective: To find possible association of R1939W and P1987R variants of OTOF gene with severe to profound NSSHL in cochlear implant subjects.
Methods: It was a case control study, conducted from June 2021 to February 2022, comprising 50 cases of severe to profound NSSHL who had received cochlear implant from ENT Department, CMH Rawalpindi and 50 age-matched healthy controls from PEMH Rawalpindi. Blood samples were collected from all the subjects, followed by DNA extraction and allele-specific polymerase chain reaction, performed at Multi-disciplinary Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using ‘SPSS’ and ‘XLSTAT’, followed by genetic analysis using ‘SNPstat’.
Results: Mean age of the cases was 5.96 ± 4.62 years (N=50), comprising 58% males and 42% females. All had bilateral and prelingual HL. Parental consanguinity was 72%, whereas 62% cases had a positive family history of deafness. Alleles of R1939W and P1987R were not associated with NSSHL, as shown by their p values of 0.56 and 0.89 respectively. For R1939W ORs were 0.71 (dominant model) and 0.80 (overdominant model), indicating negative association with NSSHL. Regarding P1987R OR was 0.96 (log-additive model). Genotypes of both variants were not in HW Equilibrium (p <0.0001), whereas their alleles showed high LD (D’=0.92).
Conclusion: High percentage of parental consanguinity was observed among cochlear implant candidates. The OTOF variants R1939W and P1987R were found to have protective roles against NSSHL in study population.
doi: https://doi.org/10.12669/pjms.39.5.6393
How to cite this: Naseer H, Rashid A, Majeed A, Baig ZA. Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects. Pak J Med Sci. 2023;39(5):---------. doi: https://doi.org/10.12669/pjms.39.5.6393
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.