bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning–augmented objective functional testing in the degenerative spine: quantifying impairment using patient-specific five-repetition sit-to-stand assessment
Authors: Staartjes Victor E. , Klukowska Anita M. , Vieli Moira , Niftrik Christiaan H. B. van , Stienen Martin N. , Serra Carlo , Regli Luca , Vandertop W. Peter , Schröder Marc L. 
Published: November 2021

OBJECTIVE
What is considered “abnormal” in clinical testing is typically defined by simple thresholds derived from normative data. For instance, when testing using the five-repetition sit-to-stand (5R-STS) test, the upper limit of normal (ULN) from a population of spine-healthy volunteers (10.5 seconds) is used to identify objective functional impairment (OFI), but this fails to consider different properties of individuals (e.g., taller and shorter, older and younger). Therefore, the authors developed a personalized testing strategy to quantify patient-specific OFI using machine learning.

METHODS
Patients with disc herniation, spinal stenosis, spondylolisthesis, or discogenic chronic low-back pain and a population of spine-healthy volunteers, from two prospective studies, were included. A machine learning model was trained on normative data to predict personalized “expected” test times and their confidence intervals and ULNs (99th percentiles) based on simple demographics. OFI was defined as a test time greater than the personalized ULN. OFI was categorized into types 1 to 3 based on a clustering algorithm. A web app was developed to deploy the model clinically.

RESULTS
Overall, 288 patients and 129 spine-healthy individuals were included. The model predicted “expected” test times with a mean absolute error of 1.18 (95% CI 1.13–1.21) seconds and R2 of 0.37 (95% CI 0.34–0.41). Based on the implemented personalized testing strategy, 191 patients (66.3%) exhibited OFI. Type 1, 2, and 3 impairments were seen in 64 (33.5%), 91 (47.6%), and 36 (18.8%) patients, respectively. Increasing detected levels of OFI were associated with statistically significant increases in subjective functional impairment, extreme anxiety and depression symptoms, being bedridden, extreme pain or discomfort, inability to carry out activities of daily living, and a limited ability to work.

CONCLUSIONS
In the era of “precision medicine,” simple population-based thresholds may eventually not be adequate to monitor quality and safety in neurosurgery. Individualized assessment integrating machine learning techniques provides more detailed and objective clinical assessment. The personalized testing strategy demonstrated concurrent validity with quality-of-life measures, and the freely accessible web app (https://neurosurgery.shinyapps.io/5RSTS/) enabled clinical application.
Impact of Molecular Subtypes of Breast Cancer on Axillary Lymph Node Metastasis: A Tertiary Center Experience
Authors: Singh Dharmendra , Mukherjee Soumen 
Published: November 2021

Background: Axillary lymph node metastasis (ALNM) is one of the important prognostic factors of breast cancer. The objective of this study was to assess the risk of ALNM in different molecular subtypes determined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (her2neu) of breast cancer.
Methods: This retrospective study was conducted on patients who had undergone upfront breast conserving surgery (BCS) or modified radical mastectomy (MRM). Patients were classified as HR (hormone receptor) +/ her2neu- (ER or PR positive and her2neu negative), HR+/her2neu+ (ER or PR positive and her2neu positive), HR-/her2neu- (ER, PR and her2neu negative or triple negative or basal type), and HR-/her2neu+ (ER or PR negative and her2neu positive). The association between clinicopathological variables and ALNM was evaluated in logistic regression analyses.
Results: In this study, 476 patients met the inclusion criteria, and had 67.2% ALNM at diagnosis. ALNM was statistically significantly correlated with age ≤ 40 years (p=0.026), tumor grade (p=0.007), pathological tumor size (P<0.001), estrogen receptor (P=0.045), molecular subtypes (P=0.021), LVI (P<0.001), and PNI (P<0.001). Post Hoc test revealed that HR-/her2neu+ subtypes of breast cancer had the highest and HR+/her2neu- had the lowest risk of ALNM.
Conclusion: ALNM may be predicted by molecular subtypes of breast cancer. The risk of ALNM is less in TNBC although it is clinically more aggressive. These findings may play an important role in gauging the individualized axillary management in breast cancer.
Spindle Cell Carcinoma of the Breast: A Case Report Representing Diagnostics, Therapeutics, Intervention, and Outcome
Authors: Naser Athamnah Mohammad , M. Al-Barrak Shatha , A. Rabai Nimah , Natelauri Tea , S O Al Azzam Hussein , Alorjani Mohammed , M. Al-Rusan Omar , Abu-Shanab Amer 
Published: November 2021

Background: Spindle cell carcinoma (SpCC) is an unusual form of squamous cell carcinoma (SCC) and can sometimes present in the breast. Owing to the rarity of breast SpCC, few case studies are available nowadays and proper evidence is scarce.
Case presentation: We herein report a 60-year-old female patient, who was referred to the surgery services after presenting with a right breast ulcerated mass. On physical examination, a 7x7 cm mass was found along with a 3 cm ulcer on the top of it. Both mammography and ultrasound showed a dense mass, and tru-cut and skin punch biopsies confirmed neoplastic spindle cells within the lesion. The patient underwent a right total mastectomy with sentinel lymph node biopsies with no further chemotherapy or radiotherapy.
Conclusion: Owing to the heterogeneity of SpCC, there is no exact treatment protocol for this type of cancer, and mastectomy or conservative surgery can be performed in certain groups of patients depending on tumor size, stage, and lymph node involvement. Fortunately, promising medical and biological therapies might be of use in the near future.
Economic ECONOMIC REVITALIZATION PROGRAM in ACHIEVING THE HAZE-FREE ASEAN TARGET 2020 by THE RIAU PROVINCE’S PEATLAND RESTORATION AGENCY
Authors: Nizmi Yusnarida Eka , Olivia Yessi , Retnaningsih Umi Oktyari , Saeri M. , Jama’an Ahmad , Alfajri Alfajri 
Published: November 2021

This study analyses the implementation of good governance principles for the economic revitalization program under Riau Province’s Badan Restorasi Gambut (Peatland Restoration Agency) supervision. One of the aims of this program is to support the haze-free ASEAN 2020 roadmap. Riau province is an area prone to forest fire disasters. Its peatland area, which is twice as large as Malaysia’s peatland, have a very high potential for damage due to forest fires. To mitigate the damages, BRG initiated the 3R program: Rewetting, Revegetation, and Revitalization. What makes this topic interesting is BRG emphasizes the aspects of economic empowerment of local communities to prevent further forest and peatland damages. To assess the implementation of BRG’s program, our research team conducted several interviews with representatives from Indonesia’s Ministry of Environment and Forestry, NGOs, academics, farmers, and villages’ facilitators who assisted local communities that received the BRG’s assistance packages. Our study shows that BRG’s economic revitalization program had succeeded in creating small scale economic activities such as honey industry, pineapple farming, and catfish farming. However, the ineffective coordination and communication between BRG and the local communities had prevented them from constructing an effective method to prevent future forest fires.
The Effect of Bonus Plan, Political Cost and Earning Management toward Social and Environment Disclosure Quality
Authors: Ebri Rosani Gabriella , Santosa, S.E., MAFIS, Ak. Setyarini 
Published: November 2021

<p>This research examines whether bonus plan, political cost, and earning management have influence to the social and environment disclosure quality or corporate social responsibility This research is important due to the increasing level of public awareness to the social and environmental disclosures that in turn, it can be used as part of the corporate strategy to attract the market as well as the stakeholder. There are 45 companies used as samples and are taken from the manufacturing companies listed in Indonesia Stock Exchange for the period of 2013-2017. Using multiple linear regression, the finding from this research shows that both earning management and political cost have positive significant effect towards social and environment disclosure quality, while bonus plan has insignificant effect towards social and environment disclosure quality.</p>
A Preliminary Design of a Hybrid Machine for Additive and Subtractive Manufacturing
Authors: Sutisna Nanang Ali 
Published: November 2021

<p>Additive manufacturing (AM) or commonly called 3D printing (3DP) and rapid prototyping (RP) is a technique of blending materials by either fusion, binding, or solidifying materials. Despite many advantages of AM, there is a drawback of AM such as the surface quality may not be as good as subtractive machining (SM) process, therefore it will be better to have the initial shape forming process with AM and then finishing the required surface with SM process within a single setup. This paper presents the preliminary design of hybrid AM-SM machine to process a resin based material. The design includes structural design and control design of the machine using the material and firmware widely available in the market.</p><p align="center"><strong> </strong></p><strong>Keyword: </strong>Additive, Subtractive, Manufacturing, Hybrid Machine
Violência obstétrica institucional: uma questão sobre os direitos da mulher
Authors: Moura Amanda Faber Pedro , Tomasoni Yasmin Ferrari , Guimarães Bianca Macêdo , Camargo Marília Ferreira , Borges Mariana do Prado , Markus Jandrei Rogério 
Published: November 2021

Objetivo: Esta revisão integrativa tem como objetivo compreender através da literatura como se estabeleceu o processo institucional da violência obstétrica na mulher levando em conta que este fenômeno é reconhecido através de diferentes tipos de agressões que podem ocorrer no contexto da gestação, parto, puerpério, como também em situações de aborto, pós-aborto e ciclo reprodutivo. Metodologia: Trata-se de uma revisão integrativa de literatura onde foram selecionados artigos utilizando as plataformas do SciELO, PUBMED e MEDLINE e foram escolhidos para o espaço amostral da pesquisa apenas artigos publicados em português, inglês ou espanhol e uma cartilha, que retrataram a temática referente à ocorrência da violência obstétrica e artigos publicados e indexados nos referidos bancos de dados dos últimos 21 anos. Nesta revisão integrativa, realizamos atividades de busca de informações, compilação e registro dos artigos selecionados. Resultados e discussão: A violência obstétrica ainda é uma realidade, ocorrendo principalmente com mulheres de baixa renda e escolaridade, expressando-se através de abusos verbais, procedimentos desnecessários, entre outras formas. Isso se dá pela falta de preparo da equipe de saúde, leis e a não conscientização da mulher. Conclusão: A Violência obstétrica caracteriza-se por práticas inadequadas contra a mulher no período gestacional. É notório o prejuízo psicológico a esta parturiente. Para diminuir essa realidade são necessários projetos de leis que amparam as mulheres, a conscientização das mesmas durante o pré-natal, e uma formação mais humanizada dos futuros profissionais da saúde.
Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma
Authors: He Dongsheng , Liao Shengyin , Xiao Linlin , Cai Lifang , You Mengxing , He Limei , Huang Weiming 
Published: November 2021

Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC).Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method.Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P &lt; 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P &lt; 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P &lt; 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P &lt; 0.05).Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.
Molecular Surveillance and Ex Vivo Drug Susceptibilities of Plasmodium vivax Isolates From the China–Myanmar Border
Authors: Zeng Weilin , Zhao Hui , Zhao Wei , Yang Qi , Li Xinxin , Li Xiaosong , Duan Mengxi , Wang Xun , Li Cuiying , Xiang Zheng , Chen Xi , Cui Liwang , Yang Zhaoqing 
Published: November 2021

Drug resistance in Plasmodium vivax may pose a challenge to malaria elimination. Previous studies have found that P. vivax has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the ex vivo drug susceptibilities of P. vivax isolates from the China–Myanmar border and genetic variations of resistance-related genes. A total of 46 P. vivax clinical isolates were assessed for ex vivo susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC50 (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC50 values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvmrp1 (P. vivax multidrug resistance protein 1), pvdhfr (P. vivax dihydrofolate reductase), and pvdhps (P. vivax dihydropteroate synthase) were determined by PCR and sequencing. Pvmdr1 had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. Pvmrp1 had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several pvdhfr and pvdhps mutations were relatively frequent in the studied parasite population. The pvmdr1 G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of P. vivax isolates resistant to certain antimalarial drugs at the China–Myanmar border, which demands continuous surveillance for drug resistance.
IDH1 R132C and ERC2 L309I Mutations Contribute to the Development of Maffucci’s Syndrome
Authors: Cheng Peng , Chen Kun , Zhang Shu , Mu Ke-tao , Liang Shuang , Zhang Ying 
Published: November 2021

BackgroundMaffucci’s syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate dehydrogenase type 1 (IDH1) or isocitrate dehydrogenase type 2 (IDH2) mutations are associated with Maffucci’s syndrome and Ollier disease, but the mechanisms underlying hemangiomas of the Maffucci’s syndrome is still obscure. This study aimed to determine the mechanism of hemangiomas in Maffucci’s syndrome.MethodsWe received a 26-year-old female patient with typical Maffucci’s syndrome, and exome sequencing was conducted using DNA from her peripheral blood and enchondroma tissues. Somatic mutations were characterized by a comparative analysis of exome sequences and further confirmed by the sequencing of PCR products derived from original blood and tissue samples. The mutations of an additional 69 patients with Ollier disease were further tested. The functional impacts of these somatic mutations on Maffucci’s syndrome, especially the development of hemangiomas, were evaluated.ResultsWe reported a typical case of Maffucci’s syndrome, which was confirmed by both imaging findings and pathology. Through exome sequencing of this patient’s DNA samples, we identified an R132C mutation in the isocitrate dehydrogenase type 1 (IDH1) gene and an L309I mutation in the ELKS/RAB6-interacting/CAST family member 2 (ERC2) gene in this patient. Approximately 33.3% of the clones were positive for the IDH1 R132C mutation, and 19.0% of the clones were positive for the ECR2 L309I mutation. The IDH1 R132C mutation was detected in most of the patients with Ollier disease (51/69 patients), and the mean frequency of this mutation was 63.3% in total sequence readouts, but the ECR2 L309I mutation was absent in all of the patients with Ollier disease. In vitro experiments confirmed that the IDH1 R132C mutation promotes chondrocyte proliferation, and the ERC2 L309I mutation enhances angiogenesis.ConclusionsOur results suggest that while IDH1 is a known pathogenic gene in enchondromatosis, ERC2 is a novel gene identified in Maffucci’s syndrome. The somatic L309I mutation of ERC2 contributes to the pathogenesis of hypervascularization to facilitate the development of hemangiomas in Maffucci’s syndrome. The combination of the IDH1 R132C and ERC2 L309I mutations contributes to the development of Maffucci’s syndrome, and these results may enable further research on the pathogenesis of Maffucci’s syndrome.
Identification and Analysis of Small Interfering RNAs Associated With Heat Stress in Flowering Chinese Cabbage Using High-Throughput Sequencing
Authors: Ahmed Waqas , Xia Yanshi , Li Ronghua , Zhang Hua , Siddique Kadambot H.M , Guo Peiguo 
Published: November 2021

Endogenous small interfering RNAs (siRNAs) are substantial gene regulators in eukaryotes and play key functions in plant development and stress tolerance. Among environmental factors, heat is serious abiotic stress that severely influences the productivity and quality of flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee). However, how siRNAs are involved in regulating gene expression during heat stress is not fully understood in flowering Chinese cabbage. Combining bioinformatical and next-generation sequencing approaches, we identified heat-responsive siRNAs in four small RNA libraries of flowering Chinese cabbage using leaves collected at 0, 1, 6, and 12 h after a 38°C heat-stress treatment; 536, 816, and 829 siRNAs exhibited substantial differential expression at 1, 6, and 12 h, respectively. Seventy-five upregulated and 69 downregulated differentially expressed siRNAs (DE-siRNAs) were common for the three time points of heat stress. We identified 795 target genes of DE-siRNAs, including serine/threonine-protein kinase SRK2I, CTR1-like, disease resistance protein RML1A-like, and RPP1, which may play a role in regulating heat tolerance. Gene ontology showed that predictive targets of DE-siRNAs may have key roles in the positive regulation of biological processes, organismal processes, responses to temperature stimulus, signaling, and growth and development. These novel results contribute to further understanding how siRNAs modulate the expression of their target genes to control heat tolerance in flowering Chinese cabbage.
Spontaneous Intracranial Hypotension Without CSF Leakage—Concept of a Pathological Cranial to Spinal Fluid Shift
Authors: Goldberg Johannes , Häni Levin , Jesse Christopher Marvin , Zubak Irena , Piechowiak Eike I. , Gralla Jan , Dobrocky Tomas , Beck Jürgen , Raabe Andreas 
Published: November 2021

Objective: Spontaneous intracranial hypotension (SIH) is typically caused by CSF leakage from a spinal dural tear, a meningeal diverticulum, or a CSF venous fistula. However, some patients present with classic orthostatic symptoms and typical intracranial imaging findings without evidence of CSF leakage despite repeated diagnostic work-up. This article aims to elaborate a hypothesis that would explain a pathologically increased orthostatic shift of CSF from the cranial to the spinal compartment in the absence of a CSF leak.Medical Hypothesis: The symptoms of SIH are caused by a decrease in intracranial CSF volume, intracranial hypotension, and downward displacement of intracranial structures. A combination of pathologically increased spinal compliance, decreased intracranial CSF volume, low CSF outflow resistance, and decreased venous pressure might result in a pathological orthostatic cranial-to-spinal CSF shift. Thus, in rare cases, intracranial hypotension may occur in the absence of CSF leakage from the dural sac.Conclusion: We propose a pathophysiological concept for the subgroup of SIH patients with typical cranial imaging findings and no evidence of CSF leakage. In these patients, reducing the compliance or the volume of the spinal compartment seems to be the appropriate therapeutic strategy.