bluuebunny/crossref_metadata_2025 huggingface dataset:
A scoping review of the changing landscape of geriatric medicine in undergraduate medical education: curricula, topics and teaching methods
Authors: Masud Tahir , Ogliari Giulia , Lunt Eleanor , Blundell Adrian , Gordon Adam Lee , Roller-Wirnsberger Regina , Vassallo Michael , Mari Daniela , Kotsani Marina , Singler Katrin , Romero-Ortuno Roman , Cruz-Jentoft Alfonso J. , Stuck Andreas E.
Published: January 2022

Purpose

The world’s population is ageing. Therefore, every doctor should receive geriatric medicine training during their undergraduate education. This review aims to summarise recent developments in geriatric medicine that will potentially inform developments and updating of undergraduate medical curricula for geriatric content.

Methods

We systematically searched the electronic databases Ovid Medline, Ovid Embase and Pubmed, from 1st January 2009 to 18th May 2021. We included studies related to (1) undergraduate medical students and (2) geriatric medicine or ageing or older adults and (3) curriculum or curriculum topics or learning objectives or competencies or teaching methods or students’ attitudes and (4) published in a scientific journal. No language restrictions were applied.

Results

We identified 2503 records and assessed the full texts of 393 records for eligibility with 367 records included in the thematic analysis. Six major themes emerged: curriculum, topics, teaching methods, teaching settings, medical students’ skills and medical students’ attitudes. New curricula focussed on minimum Geriatrics Competencies, Geriatric Psychiatry and Comprehensive Geriatric Assessment; vertical integration of Geriatric Medicine into the curriculum has been advocated. Emerging or evolving topics included delirium, pharmacotherapeutics, healthy ageing and health promotion, and Telemedicine. Teaching methods emphasised interprofessional education, senior mentor programmes and intergenerational contact, student journaling and reflective writing, simulation, clinical placements and e-learning. Nursing homes featured among new teaching settings. Communication skills, empathy and professionalism were highlighted as essential skills for interacting with older adults.

Conclusion

We recommend that future undergraduate medical curricula in Geriatric Medicine should take into account recent developments described in this paper. In addition to including newly emerged topics and advances in existing topics, different teaching settings and methods should also be considered. Employing vertical integration throughout the undergraduate course can usefully supplement learning achieved in a dedicated Geriatric Medicine undergraduate course. Interprofessional education can improve understanding of the roles of other professionals and improve team-working skills. A focus on improving communication skills and empathy should particularly enable better interaction with older patients. Embedding expected levels of Geriatric competencies should ensure that medical students have acquired the skills necessary to effectively treat older patients.
End-to-end Mars entry, descent, and landing modeling and simulations for Tianwen-1 guidance, navigation, and control system
Authors: Xu Chao , Huang Xiangyu , Guo Minwen , Li Maodeng , Hu Jinchang , Wang Xiaolei
Published: January 2022

On May 15, 2021, the Tianwen-1 lander successfully touched down on the surface of Mars. To ensure the success of the landing mission, an end-to-end Mars entry, descent, and landing (EDL) simulator is developed to assess the guidance, navigation, and control (GNC) system performance, and determine the critical operation and lander parameters. The high-fidelity models of the Mars atmosphere, parachute, and lander system that are incorporated into the simulator are described. Using the developed simulator, simulations of the Tianwen-1 lander EDL are performed. The results indicate that the simulator is valid, and the GNC system of the Tianwen-1 lander exhibits excellent performance.
Pathway of sodium alginate synthesis from marine brown algae, Sargassum wightii from Sri Lanka
Authors: Jayasinghe G. D. T. M. , Jinadasa B. K. K. K. , Sadaruwan N. A. G.
Published: January 2022

Alginates are natural polysaccharides that are extracted from brown seaweed varieties and it is widely used for their rheological properties. The main step in the extraction protocol of sodium alginate is alkaline extraction. Sodium alginate was produced by dipping the seaweed in 1% formaldehyde and 2.5% of sodium carbonate solution and properties were studied following the standard methods. The amount of sodium alginate yield was 31.7% in Sargassum wightii. The moisture content and the ash content were recorded at 16.82% and 5.20%, respectively. The viscosity and the gel strength were noted as 40 vcP, 4.54 × 10–2 kN with 0.1 M CaCl2 and 6.86 × 10–2 kN with 0.2 M CaCl2 respectively. This study of the extraction method and its properties reveal that Sargassum wightii brown seaweed species have a high affinity to extract the alginate.
Estimated glycemic index of rice increases with the release of new varieties in the middle reach of the Yangtze River
Authors: Huang Min , Xiao Zhengwu , Hu Liqin , Chen Jiana , Cao Fangbo
Published: January 2022

The amylose content of newly-released rice varieties has steadily decreased in rice-growing regions in the middle reach of the Yangtze River during 2006–2021, to parallel increasing consumption of soft-textured rice with low amylose content. We estimated the glycemic index of these newly-released rice varieties and reveal a significantly increasing trend, showing a 0.3 annual increase in estimated glycemic index of new rice varieties released each year. These results highlight the need to assess the potential health risks associated with the development of soft-textured rice with low amylose rice.
A Classification Model of Legal Consulting Questions Based on Multi-Attention Prototypical Networks
Authors: Feng Jianzhou , Cui Jinman , Wei Qikai , Zhou Zhengji , Wang Yuxiong
Published: January 2022

Text classification is a research hotspot in the field of natural language processing. Existing text classification models based on supervised learning, especially deep learning models, have made great progress on public datasets. But most of these methods rely on a large amount of training data, and these datasets coverage is limited. In the legal intelligent question-answering system, accurate classification of legal consulting questions is a necessary prerequisite for the realization of intelligent question answering. However, due to lack of sufficient annotation data and the cost of labeling is high, which lead to the poor effect of traditional supervised learning methods under sparse labeling. In response to the above problems, we construct a few-shot legal consulting questions dataset, and propose a prototypical networks model based on multi-attention. For the same category of instances, this model first highlights the key features in the instances as much as possible through instance-dimension level attention. Then it realizes the classification of legal consulting questions by prototypical networks. Experimental results show that our model achieves state-of-the-art results compared with baseline models. The code and dataset are released on https://github.com/cjm0824/MAPN.
Einzug der Computerspielstörung als Verhaltenssucht in die ICD-11
Authors: Lindenberg Katajun , Holtmann Martin
Published: January 2022

Zusammenfassung. Durch die Aufnahme der neuen Kategorie „Störungen durch süchtiges Verhalten“ in der ICD-11 wurde durch die Weltgesundheitsorganisation (WHO) offiziell anerkannt, dass belohnende Verhaltensweisen, analog zu psychotropen Substanzen, abhängig machen können. Neben der bereits in der ICD-10 gelisteten Glücksspielstörung wurde die Computerspielstörung als neue Diagnose in diese Kategorie aufgenommen. Das Erscheinungsbild ist charakterisiert durch Kontrollverlust, Priorisierung des Gamings vor anderen Aktivitäten, Fortsetzen des Gamings trotz negativer Konsequenzen sowie der Bedingung, dass durch die Symptomatik ein signifikanter Leidensdruck verursacht wird. Störungstypische Pathomechanismen umfassen konsumabhängige Faktoren, entwicklungsabhängige Faktoren, Veränderungen in der Belohnungssensitivität und -verarbeitung sowie verzerrte Belohnungserwartungen (Kognitionen). Die psychotherapeutische Versorgung von Kindern, Jugendlichen und jungen Erwachsenen mit diesem Störungsbild, die mittlerweile einen substanziellen Anteil der ambulanten Versorgung ausmachen, ist herausfordernd. Neben der Entwicklung von validen Diagnostiktools und wirksamen Therapiemethoden besteht hoher Weiterbildungsbedarf für Behandelnde in der Kinder- und Jugendpsychiatrie und -psychotherapie zu diesem neuen Störungsbild.
Klassifikation von Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen in der ICD-11
Authors: Döpfner Manfred , Banaschewski Tobias
Published: January 2022

Zusammenfassung. Der Beitrag gibt eine kurze Übersicht über die Veränderungen in der Klassifikation von Hyperkinetischen Störungen und Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen nach ICD-11 (International Statistical Classification of Diseases and Related Health Problems). Sowohl in der Bezeichnung als auch in der Binnendifferenzierung lehnt sich ICD-11 erfreulicherweise an das DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) an. Auch die Aufgabe der ICD-10-Kombinationsdiagnose der Hyperkinetischen Störung des Sozialverhaltens zugunsten von Mehrfachdiagnosen ist zu begrüßen. Der Verzicht auf eine exakte Operationalisierung der Kriterien hilft einerseits bei der Einordung von Grenzfällen in der klinischen Praxis, macht es aber auch notwendig, für die Klärung der einzelnen Symptome auf das DSM-5 zurückzugreifen.
Polarization modulation with optical lock-in detection reveals universal fluorescence anisotropy of subcellular structures in live cells
Authors: Guan Meiling , Wang Miaoyan , Zhanghao Karl , Zhang Xu , Li Meiqi , Liu Wenhui , Niu Jing , Yang Xusan , Chen Long , Jing Zhenli , Zhang Micheal Q. , Jin Dayong , Xi Peng , Gao Juntao
Published: January 2022

The orientation of fluorophores can reveal crucial information about the structure and dynamics of their associated subcellular organelles. Despite significant progress in super-resolution, fluorescence polarization microscopy remains limited to unique samples with relatively strong polarization modulation and not applicable to the weak polarization signals in samples due to the excessive background noise. Here we apply optical lock-in detection to amplify the weak polarization modulation with super-resolution. This novel technique, termed optical lock-in detection super-resolution dipole orientation mapping (OLID-SDOM), could achieve a maximum of 100 frames per second and rapid extraction of 2D orientation, and distinguish distance up to 50 nm, making it suitable for monitoring structural dynamics concerning orientation changes in vivo. OLID-SDOM was employed to explore the universal anisotropy of a large variety of GFP-tagged subcellular organelles, including mitochondria, lysosome, Golgi, endosome, etc. We found that OUF (Orientation Uniformity Factor) of OLID-SDOM can be specific for different subcellular organelles, indicating that the anisotropy was related to the function of the organelles, and OUF can potentially be an indicator to distinguish normal and abnormal cells (even cancer cells). Furthermore, dual-color super-resolution OLID-SDOM imaging of lysosomes and actins demonstrates its potential in studying dynamic molecular interactions. The subtle anisotropy changes of expanding and shrinking dendritic spines in live neurons were observed with real-time OLID-SDOM. Revealing previously unobservable fluorescence anisotropy in various samples and indicating their underlying dynamic molecular structural changes, OLID-SDOM expands the toolkit for live cell research.
Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison
Authors: Li Yuchen , Sjölander Arvid , Song Huan , Cnattingius Sven , Fang Fang , Yang Qian , Fernández de la Cruz Lorena , Mataix-Cols David , Brander Gustaf , Li Jiong , Zhang Wei , Fall Katja , D’Onofrio Brian M. , Almqvist Catarina , Lichtenstein Paul , Valdimarsdóttir Unnur A. , Lu Donghao
Published: January 2022

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973–2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32–36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.12] and sibling analyses (HR 1.10, 95% CI 1.02–1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.
Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET
Authors: Huang Wei-Chieh , Yen Jia-Hau , Sung Yu-Wen , Tung Shiao-Lin , Chen Po-Ming , Chu Pei-Yi , Shih Ya-Chi , Chi Hsiang-Cheng , Huang Yi-Ching , Huang Shih-Jei , Wang Lu‐Hai
Published: January 2022

Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to lack of effective endocrine or targeted therapies, aggressive nature and high rate of chemoresistance. Cancer stem cells (CSCs) are considered to play critical roles in cancer recurrence and chemoresistance. THEMIS2 was identified as the sole common elevated gene in three triple negative breast cancer (TNBC) and two ovarian CSC lines. We discovered an intrinsic signaling scaffold function of THEMIS2, which acts as a novel regulator of cancer stemness in promoting multiple cancer stemness properties including sphere formation, stemness markers expression, chemoresistance and tumorigenicity with low numbers of cancer cells implantation. For the first time, we demonstrated that THEMIS2 specifically enhanced MET activating phosphorylation by suppressing the association of protein-tyrosine phosphatases 1B (PTP1B) with p-MET and MET, which accounted mainly for THEMIS2-mediated effect on cancer stemness and chemoresistance. Increased THEMIS2 expression was associated with poor survival in TNBC patients and in patients from our breast cancer cohort. We found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. Notably, stable overexpression of THEMIS2 is associated with enhanced sensitivity toward Capmatinib and CPT treatment. Expression levels of THEMIS2 and p-MET protein were positively correlated in the 465 breast cancer specimens. Our study revealed the novel oncogenic role of THEMIS2 and its underlying mechanism via suppressing PTP1B association with MET and thus leading to its activation. Our findings suggest that THEMIS2 could be a biomarker for MET targeted therapy and also provide a potential clinical application using low dosages of CPT for treatment of THEMIS2 positive TNBC.
Novel insights into the consequences of obesity: a phenotype-wide Mendelian randomization study
Authors: He Chang , Zhang Miaoran , Li Jiuling , Wang Yiqing , Chen Lanlan , Qi Baiyu , Wen Jianping , Yang Jianli , Lin Sitong , Liu Dianyuan , Dong Ying , Wang Liying , Wang Qing , Chen Peng
Published: January 2022

Obesity is thought to significantly impact the quality of life. In this study, we sought to evaluate the health consequences of obesity on the risk of a broad spectrum of human diseases. The causal effects of exposing to obesity on health outcomes were inferred using Mendelian randomization (MR) analyses using a fixed effects inverse-variance weighted model. The instrumental variables were SNPs associated with obesity as measured by body mass index (BMI) reported by GIANT consortium. The spectrum of outcome consisted of the phenotypes from published GWAS and the UK Biobank. The MR-Egger intercept test was applied to estimate horizontal pleiotropic effects, along with Cochran’s Q test to assess heterogeneity among the causal effects of instrumental variables. Our MR results confirmed many putative disease risks due to obesity, such as diabetes, dyslipidemia, sleep disorder, gout, smoking behaviors, arthritis, myocardial infarction, and diabetes-related eye disease. The novel findings indicated that elevated red blood cell count was inferred as a mediator of BMI-induced type 2 diabetes in our bidirectional MR analysis. Intriguingly, the effects that higher BMI could decrease the risk of both skin and prostate cancers, reduce calorie intake, and increase the portion size warrant further studies. Our results shed light on a novel mechanism of the disease-causing roles of obesity.
Recent advances in nanotechnology-based COVID-19 vaccines and therapeutic antibodies
Authors: Du Lanying , Yang Yang , Zhang Xiujuan , Li Fang
Published: January 2022

This review summarizes the nanotechnology-based COVID-19 vaccines and therapeutics, including protein nanoparticle-based vaccines, lipid nanoparticle-formulated mRNA vaccines, and nanobodies as unique therapeutic antibodies.
Defect-rich walnut-like copper-doped Ni(PO3)2 catalyst towards ammonia borane electrooxidation reaction with high performance
Authors: Yu Jia , Jing Haiyan , Zhao Peng , Lu Keren , Song Juanjuan , Wu Zongdeng , Wu Haoxuan , Liu Boyuan , Lei Wu , Hao Qingli
Published: January 2022

Cu doped Ni(PO3)2 was applied as an electrocatalyst to ABOR for the first time, which showed an excellent electrocatalytic activity due to the optimized electronic structure and the increased active sites induced by the Cu doping.
A novel partitioned matrix‐based parameter update method embedded in variational Bayesian for underwater positioning
Authors: Huang Haoqian , Tang Jiacheng , Wang Manyi , Wang Bing , He Xiufeng
Published: January 2022

In order to meet the requirements of the high‐precision positioning for the autonomous underwater vehicles (AUVs) in the complex and time‐varying marine environments, a novel partitioned matrix‐based parameter update method embedded in variational Bayesian (PMPU‐VB) is proposed to deal with the positioning accuracy problem caused by the inaccurate predicted error covariance and measurement noise matrices. By employing the variational Bayesian (VB) method, the accurate predicted error covariance matrix and the measurement noise matrix can be obtained. Subsequently, the PMPU‐VB, which employs the accurate predicted error covariance matrix and measurement noise matrix, is used as a substitute of the traditional Gaussian filtering (GF) algorithm, to update the probability density function (PDF) of the state vector. The state vector is defined to follow the Gaussian distribution, and the parameters of the Gaussian distribution are deduced by using the proposed partitioned matrix‐based parameter update method. Finally, the accurate position information of the AUV can be obtained. Therefore, the more precise state vector and the error covariance matrix are acquired. The experiments results illustrate that the PMPU‐VB has higher estimate accuracy, better stability and robustness than other comparison algorithms.
Multiple stellar populations in Schwarzschild modeling and the application to the Fornax dwarf
Authors: Kowalczyk Klaudia , Łokas Ewa L.
Published: January 2022

Dwarf spheroidal (dSph) galaxies are believed to be strongly dark matter dominated and thus are considered perfect objects to study dark matter distribution and test theories of structure formation. They possess resolved, multiple stellar populations that offer new possibilities for modeling. A promising tool for the dynamical modeling of these objects is the Schwarzschild orbit superposition method. In this work we extend our previous implementation of the scheme to include more than one population of stars and a more general form of the mass-to-light ratio function. We tested the improved approach on a nearly spherical, gas-free galaxy formed in the cosmological context from the Illustris simulation. We modeled the binned velocity moments for stars split into two populations by metallicity and demonstrate that in spite of larger sampling errors the increased number of constraints leads to significantly tighter confidence regions on the recovered density and velocity anisotropy profiles. We then applied the method to the Fornax dSph galaxy with stars similarly divided into two populations. In comparison with our earlier work, we find the anisotropy parameter to be slightly increasing, rather than decreasing, with radius and more strongly constrained. We are also able to infer anisotropy for each stellar population separately and find them to be significantly different.
Limb reconstruction in a resource-limited environment
Authors: Ferreira Nando , Sabharwal Sanjeev , Hosny Gamal Ahmed , Sharma Hemant , Johari Ashok , Nandalan Vasudevan P. , Vivas Mauro , Parihar Mangal , Nayagam Selvadurai , Ferguson David , Rölfing Jan Duedal
Published: January 2022

Introduction: Limb salvage and reconstruction are often challenging and even more so in the limited resource setting. The purpose of this narrative review is to explore the strategies for addressing the unique obstacles and opportunities of limb reconstructive surgery in resource-limited environments globally. Methods: We review (1) the global burden and dimension of the problem, (2) the relevance of orthopedic forums and communication, (3) free and open-access software for deformity analysis and correction, (4) bidirectional learning opportunities, and the value of fellowships and mentoring between resource-rich and resource-limited countries, and (5) how societies like SICOT can help to tackle the problem. Finally, case examples are presented to demonstrate the choice of surgical implants, their availability in regions with limited resources, and how the universal principles of limb reconstruction can be applied, irrespective of resource availability. Results: Limb reconstruction can often be life-changing surgery with the goals of limb salvage, improved function, and ambulation. The contradiction of relatively few severe limb deformities in high-income countries (HICs) with abundant resources and the considerable burden of limb deformities in resource-limited countries is striking. Free, open access to education and software planning tools are of paramount importance to achieve this goal of limb reconstruction. Bidirectional learning, i.e., knowledge exchange between individual surgeons and societies with limited and abundant resources, can be reached via fellowships and mentoring. The presented cases highlight (1) fixator-assisted wound closure obliviating the need for plastic surgery, (2) open bone transport, and (3) hinged Ilizarov frames for correction of severe deformities. These cases underline that optimal clinical outcome can be achieved with low-cost and readily available implants when the principles of limb reconstruction are skillfully applied. Discussion: Limb lengthening and reconstruction are based on universally applicable principles. These have to be applied regardless of the planning tool or surgical implant availability to achieve the goals of limb salvage and improved quality of life.
Correlation of Nuclear Morphometry with Clinicopathologic Parameters in Malignant Breast Aspirates
Authors: Kalhan Shivani , Garg Shilpa , Satarkar Rahul N. , Sharma Puja , Hasija Sonia , Sharma Sonia
Published: January 2022

Background Nuclear size, shape, chromatin pattern, and nucleolar size and number have all been reported to change in breast cancer.

Aim The aim of the study was to quantify nuclear changes on malignant breast aspirates using morphometry and to correlate the morphometric parameters with clinicopathologic features such as cytologic grade, tumor size, lymph node status, mitotic index, and histopathologic grade.

Materials and Methods Forty-five cases of carcinoma breast diagnosed on cytology were included in this study. Cytologic grading was performed as per the Robinson's cytologic grading system. Nuclear morphometry was done on Papanicolaou stained smears. One hundred nonoverlapping cells per case were evaluated. Both geometrical and textural parameters were evaluated.

Results Comparison of cytologic grades with most morphometric features (nuclear area, perimeter, shape, long axis, short axis, intensity, total run length, and TI homogeneity) was highly significant on statistical analysis. Correlation with tumor size yielded significant results for nuclear area, perimeter, long and short axes, and intensity with p < 0.05. The study of lymph node status and morphometry showed a highly significant statistical association with all the parameters. Mitotic count was significantly associated with all the geometric parameters and one textural parameter (total run length). On correlation of ductal carcinoma in situ and histopathological Grades 1 to 3 with morphometry, it was found that all the parameters except long–run emphasis were highly significant with p < 0.001.

Conclusion Morphometry as a technique holds immense promise in prognostication in breast carcinoma.
Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck: A Tertiary Cancer Center Experience
Authors: Pareek Ananya , Patel Apurva A. , Kumar Mukesh , Kuttikat Philip G. , Annadanam Harshavardhan , Pendse Shantanu , Mohammed Naseer , Panchal Harsha P.
Published: January 2022

Background Immunotherapy is a proven therapeutic option in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum therapy. At present, there are no published Indian data regarding administration of nivolumab in this setting.

Aim The aim of this study is to retrospectively evaluate the efficacy and toxicity of nivolumab in R/M HNSCC among Indian patients who progressed after one or more lines of chemotherapy, including platinum agents.

Methods All patients of R/M HNSCC who received nivolumab between 2/6/2018 to 31/3/2020 were assessed retrospectively for the efficacy and toxicity of nivolumab therapy.

Statistical Analysis All the data analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Descriptive analysis was performed to obtain baseline characteristic of the study sample. Survival analysis was done using the Kaplan–Meier method.

Results Nivolumab therapy was tolerated well, with no new safety concerns, except one (8.3%) patient experienced grade ¾ toxicity (gastrointestinal). The clinical benefit rate (CBR) was found to be 66.7%. The median progression-free survival (PFS) was 3 months (95% CI; 2.093–3.907), and median overall survival (OS) was 8 months (95% CI; 3.731–12.269) from the date of first dose of nivolumab.

Conclusions In our study, efficacy and toxicity were comparable with international data with no new safety concerns. Nivolumab emerged as an astonishing treatment option with tolerable toxicity profile in patients with R/M HNSCC postplatinum therapy, although limited treatment options are available at present.
Study of Gemcitabine Plus Nab-Paclitaxel-Based Chemotherapy Regimen as First-Line Treatment in Metastatic Pancreatic Carcinoma
Authors: Domadia Kshitij , Goel Varun , Koyyala Venkata Pradeep Babu , Patnaik Nivedita , Chaudhari Krushna , Raina Shubhra , Doval D. C. , Talwar Vineet
Published: January 2022

Background The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population.

Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated.

Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment.

Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest.

Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer with Peritoneal Metastasis—Indian Experience
Authors: S.P Somashekhar , Karivedu Jyothsana , C. Rohit Kumar , Y. Ramya , Kapoor Priya , Rauthan Amit , K.R Ashwin
Published: January 2022

Introduction Peritoneal metastasis secondary to gastric cancer is associated with poor prognosis. Recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an efficacious treatment option for an otherwise palliative condition.

Methods A retrospective single institutional study of patents diagnosed with gastric carcinoma and peritoneal metastasis and treated with CRS and HIPEC from February 2015 to December 2019.

Results Sixteen patients with gastric cancer and peritoneal carcinomatosis were treated with CRS and HIPEC. Three patients underwent upfront surgery, and five patients underwent interval surgery. The mean peritoneal cancer index (PCI) was 3.5, and adequate complete cytoreduction (CC) score of 0/1 was achieved in all patients. All patients received HIPEC with mitomycin C. Major surgical complications were in 12.5% of patients. Grade I surgical site infection was present in one patient. Three patients had prolonged gastrointestinal (GI) recovery. The 30-day mortality was zero. Median follow-up time was 39 months. The median progression-free survival (PFS) was 12 months (95% conﬁdence interval [CI] 6.86–17.13). The median overall survival (OS) was 17 months (95% CI 6.36–27.64).

Conclusion Multidisciplinary treatment of perioperative chemotherapy with CRS and HIPEC is a promising treatment option, which may prolong survival in selected patients, and large randomized clinical trials are warranted for it to become standard of care.
Association Between Sensorineural Hearing Loss and Various Stages of Chronic Kidney Disease
Authors: Kotian Shashank , Naik Ashok S. , Revanasiddappa Manjunath , Goutham Maniyankode Krishnamohan
Published: January 2022

Objectives To compare the proportion of sensorineural hearing impairment (SHI) among patients of chronic kidney disease (CKD) stages 3&4 with CKD stage 5.

Materials and Methods This is a cross-sectional study of 30 patients with CKD stages 3 and 4 and 30 patients in stage 5. All patients had an audiological evaluation with pure tone audiometry.

Results Our study had 49 males (82%) and 11 females (18%), with the age ranging from 20 to 60 years (mean: 45.13 years). The mean SHI values in stage 3&4 were 28.44 dB and in CKD stage 5 was 31.22 dB. In the right ear, the mean hearing loss in stage 3, stage 4, and stage 5 was 28.17 dB, 28.67 dB, and 31.84 dB, respectively. In the left ear, the mean SHI values in stage 3, stage 4, and stage 5 were 27.05 dB, 31.89 dB, and 30.61 dB, respectively.

The mean SHI in stage 3&4 for age group 20 to 30 years was 13.66 dB, for 31 to 40 years was 26.33 dB, for 41 to 50 years was 35.18 dB, for 51 to 60 years was 37.12 dB. The mean SHI in stage 5 for the age group of 20 to 30 years was 16.48 dB, for 31 to 40 years was 28.29 dB, for 41 to 50 years was 31.82 dB, for 51 to 60 years was 34.35 dB. There was a significant correlation between hearing loss and CKD with respect to age (p < 0.001). The duration of renal illness and associated comorbidities was not a significant contributor to hearing loss in our study (p > 0.05).

Conclusion As per our study, with progression in the stage of chronic kidney disease, the hearing loss also increased indicating a possible link between the two. We also noted that the hearing loss increased with the increasing age.
Clinically Undetected Hodgkin Lymphoma Diagnosed Initially on Bone Marrow Biopsy: A Large Retrospective Observational Study from a Tertiary Care Center
Authors: Vangala Navatha , Paul Tara Roshni , Uppin Shantveer G. , Uppin Megha S. , Sadashivudu G. , Raju Y. Satyanarayana , Rao M. Nageswara
Published: January 2022

Introduction Hodgkin lymphoma (HL) involving the bone marrow (BM) is relatively rare with an incidence ranging from 4% to 18%. The incidence of primary HL of marrow is 0.25%. To the best of our knowledge, the present study is the largest study on HL diagnosed initially on marrow biopsy.

Objective To establish diagnostic criteria based on clinicopathological and histological features in HL diagnosed first on the marrow.

Materials and Methods This was a retrospective study done from January 2012 to December 2020 that included 36 cases of HL diagnosed initially on BM. Based on the presence of large mononuclear or binucleate Reed–Sternberg (RS)-like cells in a polymorphous inflammatory background, HL was suspected and immunohistochemistry (IHC) with CD15 and CD30 was done. Correlation with subsequent lymph node biopsies was done, wherever possible.

Results Fever (94.4%) was the most common symptom, followed by loss of weight (66.7%). Twenty-one cases (58.4%) had uni/bicytopenia and 15 cases (41.6%) had pancytopenia. Only one case showed suspicious mononuclear RS cells on aspirates and the rest of the cases were diagnosed on trephine biopsy alone. Trephine imprints showed variable cellularity in 13 (36%) cases. Diffuse involvement was seen in 24 cases (66.7%), and focal nodular aggregates were seen in 12 cases (33.3%). Out of 36 cases, 26 cases (19 cases on marrow and 7 cases on lymph node) were confirmed as HL with IHC. Immunophenotype of the RS cells on the marrow was CD30+/CD15+ in (6/29) (20.7%) cases, CD30+/CD15− in (7/29) (24.1%) cases and CD30−/CD15+ in (6/29) (20.7%) cases. Seven cases (26.9%) were diagnosed on subsequent lymph node biopsy as mixed cellularity HL with IHC confirmation. Marrow fibrosis was seen in 16 cases (44.4%), and granulomas were seen in 8 cases (22.2%).

Conclusion In cases presenting with long-standing fever and cytopenias, HL must always be suspected, even if there are no palpable lymph nodes. Bone marrow biopsy is preferable over aspiration in such cases and IHC plays a major role in diagnosing the cases.
Ischemic Stroke in Young Adults Caused by Cervical Artery Dissection—A Retrospective Study
Authors: Jazbec Lucija , Menih Marija , Arh Rok
Published: January 2022

Background Ischemic stroke is one of the most common causes of death and disability. The most common independent cause is cervical artery dissection, which represents around 20% of all cases of ischemic stroke in young adults. Risk factors for dissection include male gender, migraine (particularly with aura), hyperhomocysteinemia, recent infection, recent history of minor cervical trauma, young age, current smoking status, increased leucocyte count, and shortened activated partial thromboplastin time, whereas hypercholesterolemia and being overweight appear protective.

Patients and Methods This retrospective study was based on data of all patients aged 18 to 49 who were hospitalized in the University Medical Centre Maribor for ischemic stroke between 2010 and 2019 inclusive. The results of the research were analyzed by IBM SPSS Statistics 28 software. For statistical significance, a cut-off value of p < 0.05 was used.

Results The study includes 196 patients with 198 events of ischemic stroke. Dissection of cervical arteries was presented in 16 (8.2%) cases. The presence of arterial hypertension proved to have a relation with the presence of a dissection; patients with dissection are less likely to suffer from arterial hypertension. Duration of hospitalization in the group with dissection lasted significantly longer than in the group without dissection.

Conclusions Dissection of cervical or intracranial artery is an important cause of ischemic stroke, especially in young adults. Therefore, it should be considered in young adults with presentation of stroke who lack traditional and modifiable risk factors.
Radiographic Landmarks for Ideal Port Placement in Wrist Arthroscopy
Authors: Thayer Jacob , Lee Greg , Mailey Brian
Published: January 2022

Background The placement of wrist arthroscopy portals is traditionally performed using distances from anatomic landmarks. We sought to evaluate the safety of traditional portal placement and determine if radiographic landmarks could provide an additional method of identifying tendon intervals.

Methods Six cadaveric specimens were used to evaluate the accuracy of portal placement based on anatomic and radiographic landmarks. Fluoroscopic images were used to document the location of previously described surface landmarks. Soft tissue was dissected away to identify the relationship between the transcutaneously placed portals and the extensor tendons. With soft tissue removed, tendon intervals were identified in relationship to anatomic carpal bone landmarks, and interval distances measured. Portals were then placed under radiographic imaging on the final three specimens and accuracy was examined by the removal of overlying soft tissue to confirm accurate interval placement

Results The 3,4 portal was safely placed using only surface anatomic landmarks, however the 4,5 and midcarpal ulnar (MCU) portal sites were not consistently placed in the intended tendon interval, especially in larger wrists. Radiographic interval targets for the 3,4 portal were identified at the ulnar aspect of the scaphoid and the 4,5 portal at the ulnar one-third of the lunate. The radiographic site for the MCR was located at the inferior radial one-third of the capitate and the MCU portal was located at the radial aspect of the hamate. The 6R portal radiographic landmark is at the radial aspect of the triquetrum and 6U at the ulnar aspect of the triquetrum.

Conclusion Portal placement in wrist arthroscopy based on anatomic landmarks alone can be unreliable in larger wrists. Radiographic imaging based on carpal bone landmarks provides an additional tool for consistent placement of portals in wrist arthroscopy and may limit unintended injury to extensor tendons.

Level of Evidence This is a Level VI study.
Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute
Authors: Veduruvada Ramya Lakshmi , Uppin Megha S. , Konatam Meher Lakshmi , Alugolu Rajesh , Yeramneni Vamsi Krishna , Bhattacharjee Suchanda , Saradhi Mudumba Vijaya , Irukulla Monica Malik , Rao Madhumohan , Velugonda Nagaraj
Published: January 2022

Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines.

Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up.

Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test.

Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively.

Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.
Use of Biologic Agents for Lip and Cheek Reconstruction
Authors: Depani Monal , Ferry Andrew M. , Grush Andrew E. , Moreno Tanir A. , Jones Lloyd M. , Thornton James F.
Published: January 2022

The unique requirements of reconstructing cheek defects, often with its proximity to the mobile elements of the face including the lip and the eyelid, have been met very handily with the directed and thoughtful use of biologic wound healing agents. One of the key advantages of these agents is their ability to provide coverage for the mobile elements of the cheek and the lip in patients with multiple co-morbidities. These agents are successfully used where the standard cheek closure techniques including cervicofacial advancement flap are contraindicated due to its anesthetic requirement. Additionally, lip reconstruction involves examining the lip's three anatomic layers: mucosa, muscle, and skin. The defects must be planned for reconstruction based on the involvement of these layers. This paper serves to introduce the use of biologic wound healing agents depending on the involvement of these layers. The authors provide specific illustrations of these agents based on defect location, tissue involvement, and severity of the defect to help with procedural planning to reconstruct a very aesthetically involved part of the face.
Beyond “Doing as the Romans Do”: A review of research on countercultural business practices
Authors: Caprar Dan V. , Kim Sunghoon , Walker Benjamin W. , Caligiuri Paula
Published: January 2022

There has long been a dominant logic in the international business literature that multinational corporations should adapt business practices to “fit” host cultures. Business practices that are congruent with local cultural norms have been advocated as effective and desirable, while practices that are incongruent have been deemed problematic. We examine and challenge this persistent assumption by reviewing the literature showing evidence for both benefits and acceptance of countercultural practices (i.e., practices that are seemingly incongruent with local cultural norms or values), and disadvantages and rejection of local practices. Drawing on the literature reviewed, we offer four types of theoretical (ontological, epistemological, causal, and functional) explanations as to why and when countercultural business practices might be preferred. Finally, we provide a springboard for a future research agenda on countercultural practices, centered around understanding the circumstances under which businesses and local stakeholders might benefit from the use of countercultural practices based on such factors as strategic intent, local preferences, institutional drivers, and social responsibility.
24 000 years of climate change, mapped
Authors: Miller Johanna L.
Published: January 2022

A numerical model combines with proxy temperature data to produce the most complete paleoclimate picture yet.
Single-Point And Triple-Point Queries Visibility Constrained Minimum Link Paths In Simple Polygons
Authors: Reza Zarrabi Mohammad , Moghaddam Charkari Nasrollah
Published: January 2022

We study the query version of constrained minimum link paths between two points inside a simple polygon $P$ with $n$ vertices such that there is at least one point on the path, visible from a query point. The method is based on partitioning $P$ into a number of faces of equal link distance from a point. This partitioning is essentially a link-based shortest path map. Initially, we solve this problem for two given points $s$, $t,$ and a query point $q$. Then, the proposed solution is extended to a general case for three arbitrary query points: $s$, $t$ and $q$. In the former case, we propose an algorithm with $O(n)$preprocessing time. For the latter case, we develop an algorithm with $O(n^3)$ preprocessing time. The link distance of a $q$-$visible$ path between $s$, $t$ and the path are provided in time $O(\log n)$ and $O(m+\log n)$, respectively, for the above two cases, where $m$ is the number of links.
Regularizing the 3-D teleseismic wavefield for receiver function imaging using a radial basis function
Authors: Xie Chengliang , Fang Yuanyuan , Zhang Jinhai
Published: January 2022

Receiver function is important for imaging crustal and upper-mantle discontinuities. However, sparsely scattered stations could introduce imaging artefacts or misinterpretations for complex structures. We regularize a 3-D teleseismic wavefield to reduce these artefacts using radial basis function interpolation. First, we evaluated the feasibility of wavefield regularization with several typical models using synthetic data. The results demonstrate the high reliability of our method for recovering local 2-D and 3-D structures, even when seismic stations intentionally miss 95 per cent of a uniform fine grid. Then, we applied this method to sparsely deployed stations in Northeast China. The waveforms reconstructed from surrounding stations show good consistency with the observed waveforms; furthermore, the imaging results using the regularized data are highly comparable with the reference results obtained by using a dense 2-D seismic array of 60 stations (with a spacing of 10–17 km), even though our input data were mainly contributed by only 9 stations (with an average spacing of ∼80 km). Our results show better continuity of the 3-D topography of the subsurface compared with that obtained by the traditional method. Our regularization method could significantly improve the spatial resolution of receiver function imaging for both sparse and dense distributions of seismic stations, especially for imaging relatively complex structures with lateral variations.