bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels, patterns and determinants of using reversible contraceptives for limiting family planning in India: evidence from National Family Health Survey, 2015–16
Authors: Rahaman Margubur , Singh Risha , Chouhan Pradip , Roy Avijit , Ajmer Sumela , Rana Md Juel
Published: April 2022

Background

Demand for family planning is predominantly for birth limiting rather than birth spacing in India. Despite several family planning programmes in India, the use of reversible contraception for limiting family planning has been stagnant and largely depends on female sterilization. Though many researchers have examined patterns and determinants of using modern contraception for total family planning, studies on patterns and determinants of contraceptive use for birth limiting are limited in India. This paper examines the patterns of contraceptive use for liming demand and its determinants in India.

Methods

The National Family Health Survey-4, 2015–16 data was used. Bivariate chi-square significant test and multivariate binary logistic regression model used to accomplish the study objectives.

Results

Majority of women (86.5%) satisfied limiting demand (SLD) in India; the SLD was found significantly low among the women’s age 15–19 years (53.1%) and parity 0 (42%). The satisfied limiting demand by modern reversible contraception (mrSLD) was found significantly high in age group 15–19 years (49.1%), Muslims (30.6%) and North-east region (45.4%). The satisfied limiting demand by traditional contraception (tSLD) was almost three times higher in North-east region (26.1%) than national average of India (8.7%). The women’s years of schooling, wealth status, religion and presence of son child found to be significant determinants of mrSLD. The likelihood of tSLD was found significantly high among the women who had no son child (AOR = 1.41; 95% CI:1.34, 1.48), Muslim (AOR = 1.78; 95% CI:1.70, 1.87). A considerable regional variability in levels of SLD, mrSLD and tSLD was found in India.

Conclusion

Public investment in family planning is required to promote and provide subsidized modern reversible contraception (MRC) services, especially to women from North-east region, Muslim, Scheduled tribe, poor household and who had no son child. Improving the quality and availability of MRC services in public health centre will be helpful to increase SLD among the above mentioned women. Besides, the promotion of MRC will be supportive to overcome the issues of sterilization regrets in India.
Assessing distinguishable social skills in medical admission: does construct-driven development solve validity issues of situational judgment tests?
Authors: Mielke Ina , Breil Simon M. , Amelung Dorothee , Espe Lia , Knorr Mirjana
Published: April 2022

Background

Social skills are important for future physicians and are therefore increasingly considered in selection processes. One economic assessment method from which different social skills can be inferred are Situational Judgment Tests (SJTs) in which applicants are asked to rate behavioral responses in context-relevant situations. However, traditional SJTs have so far failed to distinctively measure specified constructs. To address this shortcoming in the medical admission context, we applied a construct-driven approach of SJT development in which test development was deductively guided by agency and communion as target constructs.

Method

The final version of the construct-driven SJT includes 15 items per construct with three behavioral responses. Medical school applicants (N = 1527) completed the construct-driven SJT, a traditional SJT, and an aptitude test under high-stakes condition as part of their application. A subsample (N = 575) participated in a subsequent voluntary online study with self-report measures of personality and past behavior.

Results

The proposed two-factor structure and internal consistency of the construct-driven SJT was confirmed. Communal SJT scores were positively associated with self-reported communal personality and communal behavior, yet effects were smaller than expected. Findings for agentic SJT scores were mixed with positive small associations to self-reported agentic personality scores and agentic behavior but unexpected negative relations to communal self-reported measures.

Conclusions

Results suggest that construct-driven SJTs might overcome validity limitations of traditional SJTs, although their implementation is challenging. Despite first indicators of validity, future research needs to address practical points of application in high-stakes settings, inclusion of other constructs, and especially prediction of actual behavior before the application of construct-driven SJTs for selection purposes in medical admission can be recommended.
Ethical decision-making climate, moral distress, and intention to leave among ICU professionals in a tertiary academic hospital center
Authors: Silverman Henry , Wilson Tracey , Tisherman Samuel , Kheirbek Raya , Mukherjee Trishna , Tabatabai Ali , McQuillan Karen , Hausladen Rachel , Davis-Gilbert Melissa , Cho Eunsung , Bouchard Kerri , Dove Samantha , Landon Julie , Zimmer Michele
Published: April 2022

Background

Commentators believe that the ethical decision-making climate is instrumental in enhancing interprofessional collaboration in intensive care units (ICUs). Our aim was twofold: (1) to determine the perception of the ethical climate, levels of moral distress, and intention to leave one's job among nurses and physicians, and between the different ICU types and (2) determine the association between the ethical climate, moral distress, and intention to leave.

Methods

We performed a cross-sectional questionnaire study between May 2021 and August 2021 involving 206 nurses and physicians in a large urban academic hospital. We used the validated Ethical Decision-Making Climate Questionnaire (EDMCQ) and the Measure of Moral Distress for Healthcare Professionals (MMD-HP) tools and asked respondents their intention to leave their jobs. We also made comparisons between the different ICU types. We used Pearson's correlation coefficient to identify statistically significant associations between the Ethical Climate, Moral Distress, and Intention to Leave.

Results

Nurses perceived the ethical climate for decision-making as less favorable than physicians (p < 0.05). They also had significantly greater levels of moral distress and higher intention to leave their job rates than physicians. Regarding the ICU types, the Neonatal/Pediatric unit had a significantly higher overall ethical climate score than the Medical and Surgical units (3.54 ± 0.66 vs. 3.43 ± 0.81 vs. 3.30 ± 0.69; respectively; bothp ≤ 0.05) and also demonstrated lower moral distress scores (bothp < 0.05) and lower “intention to leave” scores compared with both the Medical and Surgical units. The ethical climate and moral distress scores were negatively correlated (r = −0.58,p < 0.001); moral distress and "intention to leave" was positively correlated (r = 0.52,p < 0.001); and ethical climate and “intention to leave” were negatively correlated (r = −0.50,p < 0.001).

Conclusions

Significant differences exist in the perception of the ethical climate, levels of moral distress, and intention to leave between nurses and physicians and between the different ICU types. Inspecting the individual factors of the ethical climate and moral distress tools can help hospital leadership target organizational factors that improve interprofessional collaboration, lessening moral distress, decreasing turnover, and improved patient care.
Cost-effectiveness of a mental health drop-in centre for young people with long-term physical conditions
Authors: Clarke Harrison , Morris Walter , Catanzano Matteo , Bennett Sophie , Coughtrey Anna E. , Heyman Isobel , Liang Holan , Shafran Roz , Batura Neha
Published: April 2022

Background

Paediatric patients being treated for long-term physical health conditions (LTCs) have elevated mental health needs. However, mental health services in the community are difficult to access in the usual course of care for these patients. The Lucy Project – a self-referral drop-in access point—was a program to address this gap by enrolling patients for low-intensity psychological interventions during their treatment for LTCs. In this paper, we evaluate the cost-effectiveness of the Lucy Project.

Methods

Using a pre-post design, we evaluate the cost-effectiveness of the intervention by calculating the base-case incremental cost-effectiveness ratio (ICER) using outcomes data and expenses recorded by project staff. The target population was paediatric patients enrolled in the program with an average age of 9 years, treated over a time horizon of 6 months. Outcome data were collected via the Paediatric Quality of Life Inventory, which was converted to health utility scores using an instrument found in the literature. The QALYs were estimated using these health utility scores and the length of the intervention. We calculate a second, practical-case incremental cost-effectiveness ratio using streamlined costing figures with maximum capacity patient enrolment within a one-year time horizon, and capturing lessons learned post-trial.

Results

The base-case model showed an ICER of £21,220/Quality Adjusted Life Years (QALY) gained, while the practical model showed an ICER of £4,359/QALY gained. The practical model suggests the intervention garners significant gains in quality of life at an average cost of £309 per patient. Sensitivity analyses reveal use of staff time was the greatest determinant of the ICER, and the intervention is cost-effective 75% of the time in the base-case model, and 94% of the time in the practical-case model at a cost-effectiveness threshold of £20,000/QALY gained.

Conclusions

We find the base-case intervention improves patient outcomes and can be considered cost-effective according to the National Institute for Health and Care Excellence (NICE) threshold of £20,000—£30,000/QALY gained, and the practical-case intervention is roughly four times as cost-effective as the base-case. We recommend future studies incorporate a control group to corroborate the effect size of the intervention.
Information needs of patients undergoing bariatric surgery in Germany: a qualitative study
Authors: Breuing Jessica , Könsgen Nadja , Doni Katharina , Neuhaus Annika Lena , Pieper Dawid
Published: April 2022

Background

Obesity is a worldwide problem with different treatment options. Bariatric surgery is an effective treatment for severe obesity; however, it leads to drastic changes (e.g., changes in everyday life and eating behavior) for patients, which may lead to information needs. Our aim was to identify the information needs of patients undergoing bariatric surgery and to explore the information provision within the healthcare process of bariatric surgery in Germany.

Methods

We conducted a qualitative study (n = 14 single, semi-structured telephone interviews) between April 2018 and April 2019. The interview guide was designed prior to the interviews and consisted of four main sections (demographic information, pre-/postoperative healthcare provision, information needs). The interviews were transcribed verbatim and analyzed using qualitative content analysis with MAXQDA software.

Results

There were unmet information needs with two factors (time: pre/postoperative and categories of information: general/specific) to be considered. Due to the patients’ description of information, we categorized information into general (different surgical procedures, general nutritional information) and specific (occurring simultaneously with a problem) information. Most patients felt well informed concerning general information. However, it was pointed out that it was not possible to provide complete information preoperatively, as the need for information only arises when there are postoperative (specific) problems. In addition, there seems to be a high demand for specific postoperative information regarding nutrition and nutrition-related problems. However, patients stated that postoperative nutritional counseling is not reimbursed by health insurance funds. The information conveyed in support groups and the exchange of experiences are highly valued by patients. However, some patients describe the information provided within the support groups as unfiltered, frightening or exaggerated.

Conclusion

Overall, there were unmet information needs. Reimbursement by health insurance funds could increase the use of postoperative nutritional counseling and thus serve existing information needs. Support groups enable an exchange of experiences and therefore offer low-barrier access to information. Cooperation between support groups and healthcare professionals in information provision could be an approach to improving existing information needs or to avoiding the development of information gaps. Furthermore, the development and implementation of a digital solution for (postoperative) information dissemination could be helpful.
Alpha-1-antichymotrypsin as a novel biomarker for diagnosis, prognosis, and therapy prediction in human diseases
Authors: Jin Yanxia , Wang Weidong , Wang Qiyun , Zhang Yueyang , Zahid Kashif Rafiq , Raza Umar , Gong Yongsheng
Published: April 2022

The glycoprotein alpha-1-antichymotrypsin (AACT), a serine protease inhibitor, is mainly synthesized in the liver and then secreted into the blood and is involved in the acute phase response, inflammation, and proteolysis. The dysregulation of AACT and its glycosylation levels are associated with tumor progression and recurrence, and could be used as a biomarker for tumor monitoring. In this review, we summarized the expression level, glycosylation modification, and biological characteristics of AACT during inflammation, neurodegenerative or other elderly diseases, and tumorigenesis, as well as, focused on the biological roles of AACT in cancer. The aberrant expression of AACT in cancer might be due to genetic alterations and/or immune by bioinformatics analysis. Moreover, AACT may serve as a diagnostic or prognostic biomarker or therapeutic target in tumors. Furthermore, we found that the expression of AACT was associated with the overall survival of patients with human cancers. Decreased AACT expression was associated with poor survival in patients with liver cancer, increased AACT expression was associated with shorter survival in patients with pancreatic cancer, and decreased AACT expression was associated with shorter survival in patients with early lung cancer. The review confirmed the key roles of AACT in tumorigenesis, suggesting that the glycoprotein AACT may serve as a biomarker for tumor diagnosis and prognosis, and could be a potential therapeutic target for human diseases.
Prognostic value and biological function of LRRN4 in colorectal cancer
Authors: Xu Cheng , Chen Yulin , Long Feiwu , Ye Junman , Li Xue , Huang Qiaorong , Yao Dejiao , Wang Xiaoli , Zhao Jin , Meng Wentong , Mo Xianming , Lu Ran , Fan Chuanwen , Zhang Tao
Published: April 2022

Background

Several nervous and nerve-related biomarkers have been detected in colorectal cancer (CRC) and can contribute to the progression of CRC. However, the role of leucine-rich repeat neuronal 4 (LRRN4), a recently identified neurogenic marker, in CRC remains unclear.

Methods

We examined the expression and clinical outcomes of LRRN4 in CRC from TCGA-COREAD mRNA-sequencing datasets and immunohistochemistry in a Chinese cohort. Furthermore, colony formation, flow cytometry, wound healing assays and mouse xenograft models were used to investigate the biological significance of LRRN4 in CRC cell lines with LRRN4 knockdown or overexpression in vitro and in vivo. In addition, weighted coexpression network analysis, DAVID and western blot analysis were used to explore the potential molecular mechanism.

Results

We provide the first evidence that LRRN4 expression, at both the mRNA and protein levels, was remarkably high in CRC compared to controls and positively correlated with the clinical outcome of CRC patients. Specifically, LRRN4 was an independent prognostic factor for progression-free survival and overall survival in CRC patients. Further functional experiments showed that LRRN4 promoted cell proliferation, cell DNA synthesis and cell migration and inhibited apoptosis. Knockdown of LRRN4 can correspondingly decrease these effects in vitro and can significantly suppress the growth of xenografts. Several biological functions and signaling pathways were regulated by LRRN4, including proteoglycans in cancer, glutamatergic synapse, Ras, MAPK and PI3K. LRRN4 knockdown resulted in downregulation of Akt, p-Akt, ERK1/2 and p-ERK1/2, the downstream of the Ras/MAPK signaling pathway, overexpression of LRRN4 leaded to the upregulation of these proteins.

Conclusions

Our results suggest that LRRN4 could be a biological and molecular determinant to stratify CRC patients into distinct risk categories, and mechanistically, this is likely attributable to LRRN4 regulating several malignant phenotypes of neoplastic cells via RAS/MAPK signal pathways.
Changing transmission dynamics among migrant, indigenous and mining populations in a malaria hotspot in Northern Brazil: 2016 to 2020
Authors: Wetzler Erica Anne , Marchesini Paola , Villegas Leopoldo , Canavati Sara
Published: April 2022

Background

Roraima state is the northernmost state in Brazil and the primary border-crossing point between Brazil and Venezuela. The uncontrolled surge of malaria in Venezuela, coupled with mass migration of Venezuelans to neighbouring countries and the upward trend in informal mining in the state, pose a serious threat to the broader region, especially to migrant, indigenous and mining populations, jeopardizing malaria elimination efforts. This study describes changes in the epidemiological profile of malaria in Roraima state related to time, place and populations at risk from 2016 to 2020.

Methods

De-identified malaria surveillance data were obtained from the Malaria Epidemiological Surveillance System from 2016 to 2020. Pearson’s chi-square tested differences between imported and autochthonous cases. Multivariable logistic regression was used to identify risk factors for imported versus autochthonous cases by demographic characteristics.

Results

Odds of being an imported case were higher for Plasmodium falciparum cases (AOR = 2.08). However, as the number of cases from Venezuela decreased in 2020 following closure of the border, the proportion of P. falciparum cases increased markedly, from 6.24% in 2019 to 18.50% in 2020. Over the 5-year period, the odds of being an imported case among miners were about nine times higher than the general population (AOR = 8.99). The proportion of total malaria cases that were among indigenous people increased from 33.09% in 2016 to 54.83% in 2020. Indigenous children had a higher burden of malaria with over 40% of cases in children 0 to 9 years old, compared to 8% in non-indigenous children 0 to 9 years old. In some municipalities, place of infection differed from place of notification, with a large proportion of cases in these municipalities reporting in Boa Vista.

Conclusions

Malaria remains a serious threat in Roraima state, especially among high-risk populations, such as miners, migrants, and indigenous people. As malaria cases have increased among indigenous people and miners, and the proportion of P. falciparum cases has increased, elimination efforts require understanding of these risk factors to tailor interventions appropriately. Furthermore, cross-border surveillance systems need to be urgently strengthened at formal and unofficial border points, especially since the border with Venezuela reopened in July 2021.
Low prevalence of Plasmodium falciparum parasites lacking pfhrp2/3 genes among asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo
Authors: Nundu Sabin S. , Arima Hiroaki , Simpson Shirley V. , Chitama Ben-Yeddy Abel , Munyeku Yannick Bazitama , Muyembe Jean-Jacques , Mita Toshihiro , Ahuka Steve , Culleton Richard , Yamamoto Taro
Published: April 2022

Background

Loss of efficacy of diagnostic tests may lead to untreated or mistreated malaria cases, compromising case management and control. There is an increasing reliance on rapid diagnostic tests (RDTs) for malaria diagnosis, with the most widely used of these targeting thePlasmodium falciparumhistidine-rich protein 2 (PfHRP2). There are numerous reports of the deletion of this gene inP. falciparumparasites in some populations, rendering them undetectable byPfHRP2 RDTs. The aim of this study was to identifyP. falciparumparasites lacking theP. falciparumhistidine rich protein 2 and 3 genes (pfhrp2/3) isolated from asymptomatic and symptomatic school-age children in Kinshasa, Democratic Republic of Congo.

Methods

The performance ofPfHRP2-based RDTs in comparison to microscopy and PCR was assessed using blood samples collected and spotted on Whatman 903™ filter papers between October and November 2019 from school-age children aged 6–14 years. PCR was then used to identify parasite isolates lackingpfhrp2/3genes.

Results

Among asymptomatic malaria carriers (N = 266), 49%, 65%, and 70% were microscopy,PfHRP2_RDT, andpfldh-qPCR positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 80% and 70% while the sensitivity and specificity of RDTs compared to microscopy were 92% and 60%, respectively. Among symptomatic malaria carriers (N = 196), 62%, 67%, and 87% were microscopy,PfHRP2-based RDT,pfldh-qPCR and positive, respectively. The sensitivity and specificity of RDTs compared to PCR were 75% and 88%, whereas the sensitivity and specificity of RDTs compared to microscopy were 93% and 77%, respectively. Of 173 samples with sufficient DNA for PCR amplification ofpfhrp2/3, deletions ofpfhrp2andpfhrp3were identified in 2% and 1%, respectively. Three (4%) of samples harboured deletions of thepfhrp2gene in asymptomatic parasite carriers and one (1%) isolate lacked thepfhrp3gene among symptomatic parasite carriers in the RDT positive subgroup. No parasites lacking thepfhrp2/3genes were found in the RDT negative subgroup.

Conclusion

Plasmodium falciparumhistidine-rich protein 2/3 gene deletions are uncommon in the surveyed population, and do not result in diagnostic failure. The use of rigorous PCR methods to identifypfhrp2/3 gene deletions is encouraged in order to minimize the overestimation of their prevalence.
Development and external validation of a novel nomogram for predicting cancer-specific survival in patients with ascending colon adenocarcinoma after surgery: a population-based study
Authors: Zhang Yi Fan , Ma Cheng , Qian Xiao Ping
Published: April 2022

Background

This study aimed to develop and validate a novel nomogram to predict the cancer-specific survival (CSS) of patients with ascending colon adenocarcinoma after surgery.

Methods

Patients with ascending colon adenocarcinoma were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015 and randomly divided into a training set (5930) and a validation set (2540). The cut-off values for age, tumour size and lymph node ratio (LNR) were calculated via X-tile software. In the training set, independent prognostic factors were identified using univariate and multivariate Cox analyses, and a nomogram incorporating these factors was subsequently built. Data from the validation set were used to assess the reliability and accuracy of the nomogram and then compared with the 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system. Furthermore, external validation was performed from a single institution in China.

Results

A total of 8470 patients were enrolled from the SEER database, 5930 patients were allocated to the training set, 2540 were allocated to the internal validation set and a separate set of 473 patients was allocated to the external validation set. The optimal cut-off values of age, tumour size and lymph node ratio were 73 and 85, 33 and 75 and 4.9 and 32.8, respectively. Univariate and multivariate Cox multivariate regression revealed that age, AJCC 8th edition T, N and M stage, carcinoembryonic antigen (CEA), tumour differentiation, chemotherapy, perineural invasion and LNR were independent risk factors for patient CSS. The nomogram showed good predictive ability, as indicated by discriminative ability and calibration, with C statistics of 0.835 (95% CI, 0.823–0.847) and 0.848 (95% CI, 0.830–0.866) in the training and validation sets and 0.732 (95% CI, 0.664–0.799) in the external validation set. The nomogram showed favourable discrimination and calibration abilities and performed better than the AJCC TNM staging system.

Conclusions

A novel validated nomogram could effectively predict patients with ascending colon adenocarcinoma after surgery, and this predictive power may guide clinicians in accurate prognostic judgement.
KIF14 affects cell cycle arrest and cell viability in cervical cancer by regulating the p27Kip1 pathway
Authors: Zhang Jie , Buranjiang Gulimire , Mutalifu Zuohelaguli , Jin Hua , Yao Liyan
Published: April 2022

Background

Cervical cancer is a kind of malignant gynecological tumor. The first choice for treating cervical cancer is still a combination of surgery and chemoradiotherapy, but the 5-year survival rate remains poor. Therefore, researchers are trying to find new ways to diagnose and treat cervical cancer early.

Methods

The expression level of KIF14 in cells and tissues was determined via qRT–PCR. The ability of the cells to proliferate, migrate, and invade was examined using CCK-8 assay kits, colony formation assays, and Transwell chambers. The expression levels of Cyclin D1, Cyclin B1, p21, and p27 were also detected using western blot assays.

Results

The results suggested that p27 is a key regulatory factor in the KIF14-mediated regulation of the cell cycle. In addition, KIF14 knockdown promotes malignancy in cervical cancer cells by inhibiting p27 degradation, resulting in cell cycle arrest.

Conclusions

KIF14 is an oncogene in cervical cancer, and knocking down KIF14 causes cell cycle arrest by inhibiting p27 degradation, thus affecting cell viability, proliferation, and migration. These results provide a potential therapeutic target for cervical cancer.
Does conventional morphological evaluation still play a role in predicting blastocyst formation?
Authors: Jiang Xiaoming , Cai Jiali , Liu Lanlan , Liu Zhenfang , Wang Wenjie , Chen Jinhua , Yang Chao , Geng Jie , Ma Caihui , Ren Jianzhi
Published: April 2022

Background

Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation.

Methods

Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles.

Results

Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77–0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771–0.789) and 0.754(95%CI: 0.745–0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911–0.94).

Conclusion

The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.
Immune activation and inflammatory biomarkers as predictors of venous thromboembolism in lymphoma patients
Authors: Otasevic Vladimir , Mihaljevic Biljana , Milic Natasa , Stanisavljevic Dejana , Vukovic Vojin , Tomic Kristina , Fareed Jawed , Antic Darko
Published: April 2022

Background

Lymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma.

Methods

The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE.

Results

The majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE.

Conclusion

Inflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.
Evaluation of multinodular goiter and primary hyperparathyroidism leads to a diagnosis of AL amyloidosis
Authors: Patel Chavez Chandani , Morales Hernandez Maria del Mar , Kresak Jesse , Woodmansee Whitney W.
Published: April 2022

Background

Amyloid goiter, defined as excess amyloid within the thyroid gland in such quantities that it produces a clinically apparent goiter, is a very rare manifestation of systemic amyloidosis with cases commonly seen in the setting of Amyloid A (AA) amyloidosis. Amyloid goiter as the primary clinical manifestation secondary to Amyloid light chain (AL) amyloidosis is very rare. We present a case of AL amyloidosis with initial manifestation as goiter with amyloid deposition in the thyroid and the parathyroid gland.

Case Presentation

A 73 year old male presented with goiter and compressive symptoms of dysphagia and hoarseness. Laboratory workup revealed normal thyroid function, nephrotic range proteinuria, elevated serum calcium level with an elevated parathyroid hormone level (PTH) consistent with primary hyperparathyroidism. Thyroid ultrasound showed an asymmetric goiter with three dominant nodules. Cervical computed tomography revealed a goiter with substernal extension and deviation of the trachea. Fine needle aspiration was unsatisfactory. There was also evidence of osteoporosis and hypercalciuria with negative Sestamibi scan for parathyroid adenoma. The patient underwent a total thyroidectomy and one gland parathyroidectomy. Pathology revealed benign thyroid parenchyma with diffuse amyloid deposition in the thyroid and parathyroid gland that stained apple green birefringence under polarized light on Congo Red stain. Immunochemical staining detected AL amyloid deposition of the lambda type. Bone marrow biopsy revealed an excess monoclonal lambda light chain of plasma cells consistent with a diagnosis of AL amyloidosis secondary to multiple myeloma affecting the kidney, thyroid, parathyroid gland, and heart. He was treated with 4 cycles of chemotherapy with a decrease in the M spike and light chains with a plan to pursue a bone marrow transplant.

Conclusion

Amyloid goiter as the primary clinical manifestation secondary to AL amyloidosis with deposition in the thyroid and parathyroid gland is rare. The top differential for amyloid deposits in the thyroid includes systemic amyloidosis or medullary thyroid carcinoma. The definitive diagnosis lies in the histopathology of the thyroid tissue. To diagnose systemic amyloidosis as the etiology for a goiter, a solid understanding of the causes of systemic amyloidosis coupled with a thorough evaluation of the patient’s history and laboratory data is necessary.
SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma
Authors: Loria Rossella , Laquintana Valentina , Scalera Stefano , Fraioli Rocco , Caprara Valentina , Falcone Italia , Bazzichetto Chiara , Di Martile Marta , Rosanò Laura , Del Bufalo Donatella , Bossi Gianluca , Sperduti Isabella , Terrenato Irene , Visca Paolo , Soddu Silvia , Milella Michele , Ciliberto Gennaro , Falcioni Rita , Ferraresi Virginia , Bon Giulia
Published: April 2022

Background

Despite the promise of dual BRAF/MEK inhibition as a therapy for BRAF-mutant (BRAF-mut) melanoma, heterogeneous responses have been observed in patients, thus predictors of benefit from therapy are needed. We have previously identified semaphorin 6A (SEMA6A) as a BRAF-mut-associated protein involved in actin cytoskeleton remodeling. The purpose of the present study is to dissect the role of SEMA6A in the biology of BRAF-mut melanoma, and to explore its predictive potential towards dual BRAF/MEK inhibition.

Methods

SEMA6A expression was assessed by immunohistochemistry in melanoma cohort RECI1 (N = 112) and its prognostic potential was investigated in BRAF-mut melanoma patients from DFCI and TCGA datasets (N = 258). The molecular mechanisms regulated by SEMA6A to sustain tumor aggressiveness and targeted therapy resistance were investigated in vitro by using BRAF-mut and BRAF-wt melanoma cell lines, an inducible SEMA6A silencing cell model and a microenvironment-mimicking fibroblasts-coculturing model. Finally, SEMA6A prediction of benefit from dual BRAF/MEK inhibition was investigated in melanoma cohort RECI2 (N = 14).

Results

Our results indicate higher protein expression of SEMA6A in BRAF-mut compared with BRAF-wt melanoma patients and show that SEMA6A is a prognostic indicator in BRAF-mut melanoma from TCGA and DFCI patients cohorts. In BRAF-mut melanoma cells, SEMA6A coordinates actin cytoskeleton remodeling by the RhoA-dependent activation of YAP and dual BRAF/MEK inhibition by dabrafenib+trametinib induces SEMA6A/RhoA/YAP axis. In microenvironment-mimicking co-culture condition, fibroblasts confer to melanoma cells a proliferative stimulus and protect them from targeted therapies, whereas SEMA6A depletion rescues the efficacy of dual BRAF/MEK inhibition. Finally, in BRAF-mut melanoma patients treated with dabrafenib+trametinib, high SEMA6A predicts shorter recurrence-free interval.

Conclusions

Overall, our results indicate that SEMA6A contributes to microenvironment-coordinated evasion of melanoma cells from dual BRAF/MEK inhibition and it might be a good candidate predictor of short-term benefit from dual BRAF/MEK inhibition.
Volunteerism during humanitarian crises: a practical guide
Authors: Bailey Heatherlee , Kaplan Lewis J.
Published: April 2022

Volunteerism to provide humanitarian aid occurs in response to disasters, crises, and conflict. Each of those volunteerism triggers engenders personal risk borne by the healthcare volunteer while rendering aid and merit specific evaluation. Factors that impact decision-making with regard to volunteering are personal, structural and crisis specific. Practical approaches to travel and on-scene safety benefit volunteers and should inform planning and preparation for volunteerism-driven travel. These approaches include planning for evacuation and potential rescue. These unique skills and approaches are generally not part of medical education outside of military service. The global medical community, including medical professional organizations, should embrace this opportunity to improve medical education and professional development to support humanitarian aid volunteerism. Disaster, crisis, or conflict-driven healthcare volunteerism highlights the core elements of altruism, dedication, and humanity that permeate clinician’s drive to render aid and save lives.
Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers
Authors: Lemma Roza Berhanu , Fleischer Thomas , Martinsen Emily , Ledsaak Marit , Kristensen Vessela , Eskeland Ragnhild , Gabrielsen Odd Stokke , Mathelier Anthony
Published: April 2022

Methylation of cytosines on DNA is a prominent modification associated with gene expression regulation. Aberrant DNA methylation patterns have recurrently been linked to dysregulation of the regulatory program in cancer cells. To shed light on the underlying molecular mechanism driving this process, we hypothesised that aberrant methylation patterns could be controlled by the binding of specific transcription factors (TFs) across cancer types. By combining DNA methylation arrays and gene expression data with TF binding sites (TFBSs), we explored the interplay between TF binding and DNA methylation in 19 cancer types. We performed emQTL (expression–methylation quantitative trait loci) analyses independently in each cancer type and identified 13 TFs whose expression levels are correlated with local DNA methylation patterns around their binding sites in at least 2 cancer types. The 13 TFs are mainly associated with local demethylation and are enriched for pioneer function, suggesting a specific role for these TFs in modulating chromatin structure and transcription in cancer patients. Furthermore, we confirmed that de novo methylation is precluded across cancers at CpGs lying in genomic regions enriched for TF binding signatures associated with SP1, CTCF, NRF1, GABPA, KLF9, and/or YY1. The modulation of DNA methylation associated with TF binding was observed at cis-regulatory regions controlling immune- and cancer-associated pathways, corroborating that the emQTL signals were derived from both cancer and tumor-infiltrating cells. As a case example, we experimentally confirmed that FOXA1 knock-down is associated with higher methylation in regions bound by FOXA1 in breast cancer MCF-7 cells. Finally, we reported physical interactions between FOXA1 with TET1 and TET2 both in an in vitro setup and in vivo at physiological levels in MCF-7 cells, adding further support for FOXA1 attracting TET1 and TET2 to induce local demethylation in cancer cells.
Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach
Authors: Neumann Alexander , Pingault Jean-Baptiste , Felix Janine F. , Jaddoe Vincent W. V. , Tiemeier Henning , Cecil Charlotte , Walton Esther
Published: April 2022

Background

DNA methylation is an epigenetic mechanism involved in human development. Numerous epigenome-wide association studies (EWAS) have investigated the associations of DNA methylation at single CpG sites with childhood outcomes. However, the overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. An estimate ofR2Methylationwould provide context regarding the importance of DNA methylation explaining variance in health outcomes. We therefore estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. We adapted a genome-based restricted maximum likelihood (GREML) approach with cross-validation (CV) to DNA methylation data and applied it in two population-based birth cohorts: ALSPAC (n = 775) and GenerationR(n = 1382).

Results

Using information from > 470,000 autosomal probes we estimated that DNA methylation at birth explains 32% (SDCV = 0.06) of gestational age variance and 5% (SDCV = 0.02) of birth weight variance. TheR2Methylationestimates for BMI, IQ and ADHD symptoms at school age estimates were near 0% across almost all cross-validation iterations.

Conclusions

The results suggest that cord blood methylation explains a moderate degree of variance in gestational age and birth weight, in line with the success of previous EWAS in identifying numerous CpG sites associated with these phenotypes. In contrast, we could not obtain a reliable estimate for school-age BMI, IQ and ADHD symptoms. This may reflect a null bias due to insufficient sample size to detect variance explained in more weakly associated phenotypes, although the trueR2Methylationfor these phenotypes is likely below that of gestational age and birth weight when using DNA methylation at birth.
Severe disseminated Veillonella parvula infection including endocarditis, bilateral psoas abscess, discitis, and osteomyelitis but sparing spinal and hip prostheses: a case report
Authors: Richards Tobias , Stephen Juan , Lui Chok Lin
Published: April 2022

Background

Veillonella species are an opportunistically pathogenic commensal anaerobic Gram-negative coccus commonly found in the oral, genitourinary, respiratory, and intestinal tract of humans and some animals. Infection is rare, even in immunocompromised hosts, and has been identified to cause a wide array of different infections, including endocarditis, osteomyelitis, and meningitis.

Case presentation

An 82-year-old Caucasian male retired ex-gymnast presented to the emergency department with a 2-week history of acute on chronic lower back pain without clear precipitant. He displayed no systemic symptoms, and had not sustained any recent injuries. Initial blood and radiological investigation did not reveal an infective or mechanical cause for his pain; however, a few days into admission, he developed a fever and signs of sepsis. A thorough septic screen was performed, including a spinal magnetic resonance imaging scan, which did not reveal any abnormalities. Blood cultures revealed Veillonella parvula bacteremia, with subsequently repeated magnetic resonance imaging displaying rapid disseminated infection including bilateral psoas abscess, discitis, and osteomyelitis. Infective endocarditis was later identified with echocardiogram. He received intravenous ceftriaxone and later oral amoxicillin and clavulanic and recovered on 6-month follow-up.

Conclusions

This case illustrates the potential pathogenicity and unexpected rapid course of Veillonella parvula infection even in an immunocompetent host presenting with back pain. This case highlights the critical importance of a thorough septic screen when investigating patients for early signs of sepsis.
Endogenous health risks, poverty traps, and the roles of health insurance in poverty alleviation
Authors: Liao Pu , Zhang Xun , Zhang Wanlu
Published: April 2022

Background

Family education investment is a key factor in reducing intergenerational transmission of poverty. At the price of higher health risk, the poor may overdraw their bodies to earn more money to invest in education. This study investigates the effect of physical overdraft, health risks and health insurance on poverty and economic growth.

Methods

This paper proposes an economic development model of endogenous health risks and poverty by setting up a physical overdraft decision. Furthermore, we introduce mutual health insurance mechanism to analyze its poverty alleviation effects.

Results

First, this study shows that health risks weaken the economy and are among the leading causes of poverty. Second, mutual health insurance can alleviate, but not completely eliminate, the negative impact of health risks on the economy. Third, appropriate health insurance arrangements can lift some or even all poor households out of poverty.

Conclusion

Health risks have a significant effect on poverty. Furthermore, health insurance mechanisms have the advantages of transferring health risks, reducing poverty and improving health equity.
Bioprospecting endophytic fungi for bioactive metabolites and use of irradiation to improve their bioactivities
Authors: El-Sayed El-Sayed R. , Hazaa Magdia A. , Shebl Magdy M. , Amer Mahmoud M. , Mahmoud Samar R. , Khattab Abeer A.
Published: April 2022

The search for new bioactive compounds with innovative modes of action and chemistry are desperately needed to tackle the increased emergence of drug-resistant microbes. With this view, this paper was conducted for the isolation, identification, and biological evaluation of fungal endophytes of eleven different plant species. A total of 69 endophytic strains were isolated and tested for the presence of bioactive metabolites with antifungal, antibacterial, anticancer, and antioxidant properties in their extracts. Upon screening, two promising strains were found to have all the before-mentioned activities. These strains were Aspergillus sydowii isolated from the bark of Ricinus communis and Aspergillus flavus isolated from the twigs of Psidium guajava. Major compounds present in extracts of the two strains were identified by GC-Mass analyses. Several well-known bioactive compounds as well as unreported ones were identified in the fungal extracts of the two strains. Furthermore, gamma irradiation (at 1000 Gy) of the fungal cultures resulted in improved bioactivities of extracts from the two strains. These findings recommend the two fungal strains as sources of antimicrobial, anticancer, and antioxidant compounds which may aid in the development of novel drugs. The presented research also explains the high-value of fungal endophytes as untapped sources of bioactive metabolites.