bluuebunny/crossref_metadata_2025 huggingface dataset:
The tyranny of meritocracy and elite higher education
Authors: Brighouse Harry
Published: July 2022

In The Tyranny of Merit, Michael Sandel argues that the American society is not meritocratic, that belief that it is causes various social harms, and that some of those harms –in particular, the costs to social solidarity – would be caused even if society actually were meritocratic. He also explores the way that the structure of higher education is implicated in the ‘ethos’ of meritocracy. This article explores just how the ethos of meritocracy might undermine solidarity, argues that the structural changes needed to achieve actual meritocracy would be benign, even though meritocracy itself is not very valuable, and identifies ways in which changes to the structure of public funding for higher education may inadvertently have undermined solidarity.
Adherence to at-Home Monitoring of Foot Temperatures in People with Diabetes at High Risk of Ulceration
Authors: Rovers F.J. , Van Netten J.J. , Busch-Westbroek T.E. , Aan de Stegge W.B. , Bus S.A.
Published: July 2022

We aimed to investigate adherence to at-home monitoring of foot temperature and its association with patient-, disease- and behavior-related factors, in people with diabetes at high risk of ulceration. We analyzed 151 participants in the enhanced therapy arm of the DIATEMP trial (all at high diabetes-related foot ulcer risk) who aimed to perform and log foot temperatures daily for 18 months or until ulceration. Adherence was the proportion of measurement days covered (PDC), with being adherent defined as PDC≥70%. If a hotspot was recorded, adherence to subsequently reducing ambulatory activity was assessed. Multivariate logistic regression analysis was performed to investigate associations with adherence. We found ninety-four participants (62.3%) adherent to measuring foot temperatures. This was higher in months 1-3 versus months 4-18: 118 (78.1%) versus 78 (57.4%; P < .001). Of 83 participants with a hotspot, 24 (28.9%) reduced ambulatory activity. Increasing age ( P = .021, OR = 1.045) and better self-care ( P = .007, OR = 1.513) were positively associated with adherence to measuring foot temperature. In conclusion, in people at high diabetes-related foot ulcer risk, adherence to measuring foot temperature was high in the first months after study commencing, but dropped over time. Adherence to reducing ambulatory activity when a hotspot was found was low over the entire study period.
The experiences of female headteachers of boys’ senior high schools in Ghana
Authors: Tangonyire Raymond , Nyame Gloria , Bediako Asare Kwame , Jangu Alhassan Amina
Published: July 2022

This study examines the experiences of the only three female headteachers leading boys’ senior high schools (SHS) in Ghana to understand the uniqueness of their career journeys, on-the-job experiences and the leadership strategies. Qualitative phenomenological approach was used for the study. The three women were interviewed multiple times over a period of five months between November 2020 and March 2021. The data were inductively and deductively analysed to identify themes that help to tell their story. The results of this study show that early exposure to role models and socialisation into the power of positive thinking at the family, school and societal levels imprint values that inspired the participants to top leadership positions and the strategies they deployed – blending of motherliness and professionalism, networking and ethical leadership. The female headteachers are bridge builders and transformational leaders who are suitable for leadership in the twenty-first century. This study identifies several implications for female headteachership including: initial preparation for aspirants of school leadership positions, ongoing professional development, and support of female school leaders. The Ministry of Education should provide women with more headteachership or leadership opportunities in schools.
Risk factors for the development of new-onset and persistent postpartum preeclampsia: A case–control study in Ghana
Authors: Fondjo Linda Ahenkorah , Amoah Beatrice , Tashie Worlanyo , Annan John Jude
Published: July 2022

Background:

Postpartum preeclampsia has been implicated in increasing hospital re-admissions, maternal morbidity, and mortality worldwide. The knowledge of the risk factors of postpartum preeclampsia would be helpful in formulating strategies to aid in the prevention, early diagnosis, and timely treatment of this disorder. Thus, this study aimed to identify the risk factors associated with the development of new-onset postpartum preeclampsia and persistent postpartum preeclampsia in the Ghanaian setting.

Methods:

This case–control study was conducted at the Obstetrics and Gynecology units of Komfo Anokye Teaching Hospital and the Kumasi Regional Hospital, both located in the Ashanti Region of Ghana. A total of 65 postpartum preeclamptic women (33 new-onset postpartum preeclampsia and 32 persistent postpartum preeclampsia) and 65 normotensive postpartum mothers were recruited from 48 h to 6 weeks post-delivery. Questionnaires were administered to assess the socio-demographic, lifestyle, obstetric characteristics, and past medical history of the study participants.

Results:

Physical inactivity ( p < 0.0001), infrequent antenatal visits ( p < 0.0001), analgesic use ( p < 0.0001), and cesarean delivery ( p = 0.021) were significantly associated with both the new-onset postpartum preeclampsia and persistent postpartum preeclampsia. Contraceptive use was significantly associated with the development of new-onset postpartum preeclampsia ( p < 0.0001) while women with low-birthweight babies are also at high risk of developing persistent postpartum preeclampsia ( p  < 0.0001).

Conclusion:

Physical inactivity, infrequent antenatal visits, analgesic use, contraceptive use, and cesarean delivery are major predisposing risk factors for the development of postpartum preeclampsia. Screening using these risk factors, close monitoring and follow-up observation of women after delivery would be beneficial in identifying and managing postpartum preeclampsia.
Impact of coronavirus 2019 pandemic on post-traumatic stress disorder symptoms among pregnant women in Jordan
Authors: Bataineh Mo’ath F , Mohamad Maysm N , Al Dhaheri Ayesha S , Rawashdeh Monketh , Al-Nawaiseh Ali M , Asali Fida F , Hashim Mona , Jarrar Amjad , Abu Jamous Dima O , Stojanovska Lily , Daour Rameez Al , Saleh Sheima T , Osaili Tareq M , Cheikh Ismail Leila
Published: July 2022

Objective:

To examine the prevalence of psychological symptoms of the coronavirus disease 2019 outbreak among pregnant women and its association with gestational age and post-traumatic stress disorder symptoms.

Methods:

A cross-sectional study was conducted between June and November 2020 to assess the impact of the COVID-19 pandemic on mental health in pregnancy using the Impact of Event Scale-Revised. Pregnant women 18 years and older were recruited from antenatal and obstetrics clinics in Jordan. A total of 481 pregnant women participated in an online survey developed on Google Forms. A self-administered structured questionnaire was used to collect sociodemographic data, mental health information, and lifestyle changes. The Impact of Event Scale-Revised, the Perceived Support Scale, and the Mental Health Lifestyle Scale were administered. Variables related to sociodemographic information and dietary behavior and perception during the COVID-19 pandemic were also assessed.

Results:

The results showed that 58.6% of pregnant women reported the presence of post-traumatic stress disorder symptoms and women in the second trimester were more likely to show post-traumatic stress disorder symptoms compared with the first and third trimesters ( p = 0.001). Moreover, a higher level of education, employment, poor dietary habits, and changes due to the pandemic were significantly associated with the Impact of Event Scale-Revised score and the presence of post-traumatic stress disorder symptoms.

Conclusion:

The COVID-19 pandemic was associated with high rates of psychological distress among pregnant women. Identifying mothers at risk of post-traumatic stress disorder symptoms may help improve maternity services and prevent adverse child outcomes.
Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer
Authors: Chang Pei-Hung , Lee Chun-Hui , Wu Tyler Min-Hsien , Yeh Kun-Yun , Wang Hung-Ming , Huang Wen-Kuan , Chan Sheng-Chieh , Chou Wen-Chi , Kuan Feng-Che , Kuo Hsuan-Chih , Kuo Yung-Chia , Hu Ching-Chih , Hsieh Jason Chia-Hsun
Published: July 2022

Background:

This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer.

Methods:

Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed.

Results:

CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis.

Conclusions:

A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.
Association of proton pump inhibitor use with survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Chen Baoqing , Yang Chen , Dragomir Mihnea P. , Chi Dongmei , Chen Wenyan , Horst David , Calin George A. , Li Qiaoqiao
Published: July 2022

Background:

Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.

Methods:

EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies.

Results:

A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17–1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation.

Conclusions:

PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.
Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study
Authors: Zhang Meng-Xia , Liu Ting , You Rui , Zou Xiong , Liu Yong-Long , Ding Xi , Duan Chong-Yang , Xu Han-Shi , Liu You-Ping , Jiang Rou , Wang Zhi-Qiang , Lin Chao , Xie Yu-Long , Chen Si-Yuan , Ouyang Yan-Feng , Xie Ruo-Qi , Hua Yi-Jun , Sun Rui , Huang Pei-Yu , Wang Shun-Lan , Chen Ming-Yuan
Published: July 2022

Background:

Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC.

Methods:

A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms.

Results:

Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death ( p < 0.001). Matched-pair analyses confirmed that LT was associated with improved OS ( p = 0.003), and the survival benefits of LT remained consistent in the subcohorts of liver and lung metastasis ( p = 0.009 and p = 0.007, respectively) but not of bone metastasis (BoM; p = 0.614). Radiotherapy was predominantly used for BoM and biological effective dose (BED) >60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy.

Conclusions:

The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.
The presence and size of intrahepatic tumors determine the therapeutic efficacy of nivolumab in advanced hepatocellular carcinoma
Authors: Kim Han Sang , Kim Chang Gon , Hong Jung Yong , Kim Il-hwan , Kang Beodeul , Jung Sanghoon , Kim Chan , Shin Sang Joon , Choi Hye Jin , Cheon Jaekyung , Chon Hong Jae , Lim Ho Yeong
Published: July 2022

Purpose:

Inter-tumoral heterogeneity at the differential lesion level raises the possibility of distinct organ-specific responses to immune checkpoint inhibitors (ICIs). We aimed to comprehensively examine the clinicopathological factors to predict and assess the efficacy of nivolumab, programmed cell death protein 1 (PD-1) blockade at an individual tumor site-specific level in patients with advanced hepatocellular carcinoma (aHCC).

Patients and Methods:

We enrolled 261 aHCC patients treated with nivolumab between 2012 and 2018. Eighty-one clinicopathological factors were comprehensively collected and analyzed. The association between all variables and survival outcomes was evaluated. According to tumor site, the organ-specific responses were assessed based on the Response Evaluation Criteria in Solid Tumors, version 1.1.

Results:

The liver was the most commonly involved organ (75.1%), followed by the lungs (37.5%) and lymph nodes (LNs, 11.5%). The liver of nonresponders was more frequently the organ of progression, while the lungs of responders were more frequently the organs of response. Among the 455 individual lesions (liver, n = 248; lung, n = 124; LN, n = 35; others including bone or soft tissues, n = 48), intrahepatic tumors showed the least response (10.1%), followed by lung (24.2%) and LN tumors (37.1%), indicating the presence of distinct organ-specific responses to nivolumab. In intrahepatic tumors, the organ-specific response rate decreased as the size increased (13% for ⩽50 mm, 8.1% for 50–100 mm, and 5.5% for >100 mm). In the subgroup analysis according to tumor location, patients with lung only metastasis (⩾30 mm) showed the best progression-free survival (PFS) and overall survival (OS). In contrast, primary HCC (⩾100 mm) without lung metastasis had the worst PFS and OS. Comprehensive analyses also revealed that liver function and systemic inflammatory indices, such as neutrophil-to-lymphocyte ratio (NLR), were significantly associated with PFS and OS.

Conclusion:

The presence and size of liver tumors, liver function, and NLR are key factors determining the response to nivolumab in aHCC. These clinical factors should be considered when treating patients with advanced HCC with PD-1 blockade.
A School Nurse and a Technology Specialist: Partnering for Improved Processes During COVID-19
Authors: Hardiman Brittany , Sonnenberg Neal
Published: July 2022

School nurses have worked tirelessly during the COVID-19 pandemic. At times, the workload has been unsustainable and there were not enough hours in the day for school nurses to complete their duties. In one school district, the high school nurse and instructional technology specialist collaborated on improving the process of collecting COVID-19 information. This resulted in dramatically reducing the amount of time it took to process information and improved the way the data were collected and shared. This article describes the steps in pandemic-related data collection and communication used before and after implementation of the improved tools and processes. The authors also provide forms, email templates, and the resulting district COVID-19 metric figures helpful to school nurses desiring to replicate the process.
Very low-dose radiation therapy for management of inflammatory myofibroblastic tumor of the lung
Authors: Najjar Nimeh , Patel Hamel , Steinberg Scott , Baskovich Brett , Rothweiler Stephanie , Hoppe Bradford
Published: July 2022

Inflammatory myofibroblastic tumor (IMT) is an uncommon chest pathology. Treatment primarily focuses on surgical resection for diagnostic and therapeutic purposes. However, there are instances in which alternative therapies with steroids, chemotherapy, or radiation are necessary. We discuss a case of recurrent IMT for which very low dose radiation proved an effective treatment.
Physical activity and the ‘pediatric inactivity triad’ in children living with chronic kidney disease: a narrative review
Authors: Wilkinson Thomas J. , O’Mahoney Lauren L. , Highton Patrick , Viana Joao L. , Ribeiro Heitor S. , Lightfoot Courtney J. , Curtis Ffion , Khunti Kamlesh
Published: July 2022

The ‘paediatric inactivity triad’ (PIT) framework consists of three complex inter-related conditions that influence physical inactivity and related health risks. In those living with chronic kidney disease (CKD), a multi-factorial milieu of components likely confound the PIT elements, resulting in a cycle of decreased physical functioning and reduced physical activity. In this review, we explore and summarize previous research on each of the three principal PIT components (exercise deficit disorder, dynapenia, and physical illiteracy) in the pediatric CKD population. We found those living with CKD are significantly physically inactive compared to their peers. Physical inactivity occurs early in the disease process and progressively gets worse as disease burden increases. Although physical activity appears to increase post-transplantation, it remains lower compared to healthy controls. There is limited evidence on interventions to increase physical activity behaviour in this population, and those that have attempted have had negligible effects. Studies reported profound reductions in muscle strength, physical performance, and cardiorespiratory fitness. A small number of exercise-based interventions have shown favourable improvements in physical function and cardiorespiratory fitness, although small sample sizes and methodological issues preclude the generalization of findings. Physical activity must be adapted and individualized to the needs and goals of the children, particularly those with acute and chronic medical needs as is the case in CKD, and further work is needed to define optimal interventions across the life course in this population if we aim to prevent physical activity declining further.
Bladder leiomyoma presenting as uterine pedunculated leiomyoma
Authors: Nazari Zeinab , Pirastehfar Zanbagh , Torabizadeh Zhila
Published: July 2022

Bladder leiomyoma is a rare benign mesothelial tumor that is more commonly reported in women. Most patients present with frequent urination or obstructive urinary symptoms. Here, we portray a 50-year-old woman who presented to the clinic with abdominal pain and vaginal bleeding. Imaging showed a lobulated mass at the posterior aspect of the urinary bladder. The pathology of the surgery demonstrated a benign mesenchymal neoplasm composed of interlacing bundles of smooth muscle fibers with a whirling pattern, which eventually confirmed bladder leiomyoma. Although this tumor is benign, it can be misdiagnosed with other diseases such as a urothelial lesion or urothelial cell carcinoma of the bladder. Accordingly, it can inevitably affect patient management. Therefore, it must be diagnosed quickly and accurately and appropriate treatment should be applied.
Transforming Primary Care in New York Through Patient-Centered Medical Homes: Findings From Qualitative Research
Authors: Weiss Linda , Griffin Kerry , Wu Meng , DeGarmo Ellie , Jasani Foram , Pagán José A.
Published: July 2022

Background:

The patient-centered medical home (PCMH) model, an important component of healthcare transformation in the United States, is an approach to primary care delivery with the goal of improving population health and the patient care experience while reducing costs. PCMH research most often focuses on system level indicators including healthcare use and cost; descriptions of patient and provider experience with PCMH are relatively sparse and commonly limited in scope. This study, part of a mixed-methods evaluation of a multi-year New York State initiative to refine and expand the PCMH model, describes patient and provider experience with New York State PCMH and its key components.

Methods:

The qualitative component of the evaluation included focus groups with patients of PCMH practices in 5 New York State counties (n = 9 groups and 67 participants) and interviews with providers and practice administrators at New York State PCMH practices (n = 9 interviews with 10 participants). Through these focus groups and interviews, we elicited first-person descriptions of experiences with, as well as perspectives on, key components of the New York State PCMH model, including accessibility, expanded use of electronic health records, integration of behavioral health care, and care coordination.

Results:

There was evident progress and some satisfaction with the PCMH model, particularly regarding integrated behavioral health and, to some extent, expanded use of electronic health records. There was less evident progress with respect to improved access and reasonable wait times, which caused patients to continue to use urgent care or the emergency department as substitutes for primary care.

Conclusions:

It is critical to understand the strengths and limitations of the PCMH model, so as to continue to improve upon and promote it. Strengths of the model were evident to participants in this study; however, challenges were also described. It is important to note that these challenges are difficult to separate from wider healthcare system issues, including inadequate incentives for value-based care, and carry implications for PCMH and other models of healthcare delivery.
A Rapid Fatal Outcome of Iliopsoas Hematoma: Clinical and Autopsy Findings
Authors: Tavone Alessandro Mauro , Giuga Gabriele , Attanasio Andrea , Petroni Giulia , Mauriello Silvestro , Cordova Francesca , Marella Gian Luca
Published: July 2022

A case of massive muscular bleeding of iliopsoas resulting in lethal exsanguination is presented. The intramuscular bleeding occurred spontaneously in an old man with heart failure, presented to the emergency department after the acute onset of shortness of breath, and treated with therapeutic doses of antiplatelets and heparin to prevent thrombosis. On the sixth day of recovery, pain in the left lumbar region develops while there was a decrease in hemoglobin level. Computed tomography (CT) scan revealed a 10 × 3 cm hematoma of the left iliac muscle. The treatment was immediately stopped, but within 6 hours, the death was confirmed. The autopsy revealed that the hematoma, and its increased size since the latest imaging assessment, was the leading cause of death. Particularly in older patients with comorbidity, even in those with clotting parameters in the therapeutic range, the potential for fatal result of iliopsoas muscle bleeding should be considered. Identifying potential patience with increased risk of this complication could be important, especially in pandemic time of COVID-19, when the use of anticoagulant therapy—both for treatment and for prevention of severe disease—has become massive and addressed also to people without previous and specific pathologies.
Nonsurgical Approach to Isolated Pancreatic Metastatic Malignant Melanoma: A Case Report and Review of the Literature
Authors: Trad George , Sheikhan Nazanin , Nguyen Andrew , Hader Ismail
Published: July 2022

Isolated pancreatic metastases from melanoma are rare with high mortality rate and account for less than 1% of metastatic melanomas. Treatment options are limited with highest overall survival reported in those with complete surgical resection. Of cases reported in the literature with nonsurgical management, highest length of survival was reported to be 10 months. We report a case of malignant melanoma with isolated pancreatic metastasis treated with interferon therapy and immunotherapy, with evidence of progressive tumor shrinkage and survival at 38 months.
A Double Whammy Pneumonia: The First Reported Case of Concurrent Neisseria meningitidis and SARS-CoV-2 Pneumonia
Authors: Valdez Michael , Sharma Rupam , Joshi Jaspreet , Sandhu Harleen , Mishra Shikha , Kuran Rasha , Heidari Arash
Published: July 2022

Meningococcal pneumonia (MP) is a rare manifestation of meningococcal disease. The MP was first described in 1907 when Neisseria meningitidis (NM) isolates were identified in sputum samples obtained from soldiers with pneumonia. Preceding and concurrent viral infections constitute a major risk for MP. During the 1918-1919 influenza pandemic, a significant increase in MP cases were reported in patients with preceding influenza infection. Despite the end of the last H1N1 influenza pandemic in 2010, seasonal influenza infections still pose a risk for simultaneous MP. History appears to be repeating itself with concomitant bacterial and viral coinfection amid the current SARS-CoV-2 pandemic. Herein presented is a unique case of an elderly woman who presented with, to the best of our knowledge, the first reported case of possible concurrent SARS-CoV-2 and MP infections.
Right Heart Failure With Recurrent Pericardial Effusion Mimicking Effusive-Constrictive Pericarditis Several Years After Renal Transplantation
Authors: Cordova Sanchez Andres , Vasigh Mostafa , Singh Ravi , May Adriana , Marvasti Mehdi , Pada Mookherjee Sakti
Published: July 2022

Pericardial disease is a rare complication after renal transplantation. We present a patient who developed high-output cardiac failure from a large arteriovenous (AV) fistula with recurrent pericardial effusion resulting in a constrictive hemodynamic pattern that was revealed during cardiac catheterization. Pericardiectomy was considered for recurrent effusive pericarditis, but per cardiac surgery recommendations, closure of the AV fistula dramatically cured the patient’s heart failure, and no recurrence of pericardial effusion was seen during follow-up almost a year later.
Case of Primary Hepatic Angiosarcoma Presenting With Jaundice and Infiltrative Liver Masses
Authors: Shaaban Adnan , Anugwom Chimaobi , Habib Alma , Mettler Tetyana , Jaffer Shahid , Thomson Mary
Published: July 2022

Primary hepatic angiosarcoma (PHA) is a rare and aggressive mesenchymal liver tumor with a poor prognosis and high mortality. Treatment options are limited to palliative chemotherapy with surgical resection reserved for the few cases that present early. We present a case of a patient who presented with jaundice and elevated liver enzymes. Imaging identified a diffusely heterogeneous liver consistent with cirrhosis, findings of portal hypertension, and 2 ill-defined liver lesions. Biopsy results confirmed PHA. Primary hepatic angiosarcoma does not have a typical presentation but should be considered for any patient presenting with an infiltrative liver mass.
Late Preterm Infant With Postnatal Diagnosis of Renal Tubular Dysgenesis
Authors: Gaffar Sheema , Arora Puneet , Ramanathan Rangasamy
Published: July 2022

A male infant born at 34 weeks’ gestation presented with acute cardiorespiratory decompensation soon after birth followed by renal failure. Initial clinical course was complicated by ventilator requirement, bilateral pneumothoraces, and hypotension managed with multiple inotropes. Persistent renal failure with oliguria and renal ultrasound showing noncystic medical renal disease prompted further investigation. Whole-exome sequencing showed 2 pathologic mutations in the angiotensin-converting enzyme (ACE) gene, suggesting a diagnosis of renal tubular dysgenesis (RTD). Renal tubular dysgenesis is usually a fatal condition affecting the renin-angiotensin system with possible autosomal recessive inheritance. Acquired cases have been described in the setting of in utero exposure to medications such as nonsteroidal anti-inflammatory medications (NSAIDs) and ACE inhibitors. Renal tubular dysgenesis should be suspected in any neonate presenting with renal failure, refractory hypotension, ventilator requirement, hypoplastic lungs, renal ultrasound showing normal-sized echogenic noncystic kidneys with poor corticomedullary differentiation, and antenatal history significant for oligohydramnios. The overall prognosis of patients with RTD continues to improve with better ventilatory management and renal replacement therapies.
Meningitis Caused by Cryptococcus neoformans in an Apparently Immunocompetent Patient
Authors: Shokouhi Shervin , Hakamifard Atousa
Published: July 2022

Cryptococcal meningitis (CM), as a life-threatening opportunistic infection, often is among cases with cell-mediated immunodeficiencies, such as AIDS, hematologic malignancies, and solid organ transplant recipients. Cryptococcal meningitis in healthy individuals is uncommon, and its detection in immunocompetent cases may be tricky because the presentation is generally more indolent than the traditional meningitis presentation, leading to late diagnosis and potential sequels. We present a CM case in an immunocompetent Iranian male patient who was treated successfully.
Corrupting Ecologically Unequal Exchange? India and Forest Loss in a Cross-National Perspective
Authors: Sommer Jamie M. , Restivo Michael , Shandra John M.
Published: July 2022

Drawing on ecologically unequal exchange theory and previous cross-national research, the authors assess whether wood exports from peripheral nations to India are related to increased forest loss in the exporting nations. The authors also build on this perspective by assessing if corruption interacts with the ecologically unequal exchange of wood exports to India. In this regard, the authors hypothesize that corruption creates an “institutional context” whereby bribes, kickbacks, and embezzlement by government officials translate into the prioritization of consumptive practices in the short term rather than advocating for long-term investments such as conservation. Toward this end, the authors expect that wood exports to India increase forest loss more in peripheral nations with higher rather than lower levels of corruption. The authors find support for this hypothesis using ordinary least squares regression for a sample of 67 low- and middle-income nations. The authors conclude by discussing the theoretical, methodological, and policy implications that follow from the interaction finding.
Strategies and inequities in balancing recreation and COVID exposure when visiting green spaces
Authors: Dass Sarina , O’Brien Daniel T. , Ristea Alina
Published: July 2022

Green spaces are beneficial for physical and mental health, especially during and after disasters. The COVID-19 pandemic, however, created a trade-off: parks could be therapeutic but also could expose people to infection. This paradox posed inequities as marginalized populations often have less access to parks and were hit harder by the pandemic. We combined cellphone-generated mobility data with demographic indicators, a neighborhood survey, and local infection rates to examine how residents of Boston, MA, navigated this trade-off in April–August 2020. We hypothesized that they adopted strategies for mitigating infection exposure—including fewer park visits and prioritizing parks that might have lower infection risk, including larger parks with more opportunity for social distancing and parks near home with fewer unfamiliar faces—but that marginalized populations would have less opportunity to do so. We also introduce a novel measure of exposure per visit based on the volume of other visitors, infection rates, and park size. Bostonians made fewer park visits relative to 2019 and prioritized larger parks and parks closer to home. These strategies varied by community. Experiences of the pandemic were influential, as communities that perceived greater risk or had more infections made more park visits, likely because they were a relatively safe activity. Communities with more infections tended to avoid nearby parks. Inequities were also apparent. Communities with more Black residents and infections had greater infection exposure per visit even when controlling for the types of parks visited, highlighting difficulties in escaping the challenges of the pandemic.
Toxicoepigenetics for Risk Assessment: Bridging the Gap Between Basic and Regulatory Science
Authors: Le Goff Anne , Louvel Séverine , Boullier Henri , Allard Patrick
Published: July 2022

Toxicoepigenetics examines the health effects of environmental exposure associated with, or mediated by, changes in the epigenome. Despite high expectations, toxicoepigenomic data and methods have yet to become significantly utilized in chemical risk assessment. This article draws on a social science framework to highlight hitherto overlooked structural barriers to the incorporation of toxicoepigenetics in risk assessment and to propose ways forward. The present barriers stem not only from the lack of maturity of the field but also from differences in constraints and standards between the data produced by toxicoepigenetics and the regulatory science data that risk assessment processes require. Criteria and strategies that frame the validation of knowledge used for regulatory purposes limit the application of basic research in toxicoepigenetics toward risk assessment. First, the need in regulatory toxicology for standardized methods that form a consensus between regulatory agencies, basic research, and the industry conflicts with the wealth of heterogeneous data in toxicoepigenetics. Second, molecular epigenetic data do not readily translate into typical toxicological endpoints. Third, toxicoepigenetics investigates new forms of toxicity, in particular low-dose and long-term effects, that do not align well with the traditional framework of regulatory toxicology. We propose that increasing the usefulness of epigenetic data for risk assessment will require deliberate efforts on the part of the toxicoepigenetics community in 4 areas: fostering the understanding of epigenetics among risk assessors, developing knowledge infrastructure to demonstrate applicability, facilitating the normalization and exchange of data, and opening the field to other stakeholders.
H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes
Authors: Kumar Amit , Datta Malabika
Published: July 2022

Background

Histone deacetylases (HDACs) that catalyze removal of acetyl groups from histone proteins, are strongly associated with several diseases including diabetes, yet the precise regulatory events that control the levels and activity of the HDACs are not yet well elucidated.

Methods

Levels of H19 and HDACs were evaluated in skeletal muscles of normal and diabetic db/db mice by Western Blot analysis. C2C12 cells were differentiated and transfected with either the scramble or H19 siRNA and the levels of HDACs and Prkab2, Pfkfb3, Srebf1, Socs2, Irs1 and Ppp2r5b were assessed by Western Blot analysis and qRT-PCR, respectively. Levels of H9, HDAC6 and IRS1 were evaluated in skeletal muscles of scramble/ H19 siRNA injected mice and chow/HFD-fed mice.

Results

Our data show that the lncRNA H19 and HDAC6 exhibit inverse patterns of expression in the skeletal muscle of diabetic db/db mice and in C2C12 cells, H19 inhibition led to significant increase in HDAC activity and in the levels of HDAC6, both at the transcript and protein levels. This was associated with downregulation of IRS1 levels that were prevented in the presence of the HDAC inhibitor, SAHA, and HDAC6 siRNA suggesting the lncRNA H19-HDAC6 axis possibly regulates cellular IRS1 levels. Such patterns of H19, HDAC6 and IRS1 expression were also validated and confirmed in high fat diet-fed mice where as compared to normal chow-fed mice, H19 levels were significantly inhibited in the skeletal muscle of these mice and this was accompanied with elevated HDAC6 levels and decreased IRS1 levels. In-vivo inhibition of H19 led to significant increase in HDAC6 levels and this was associated with a decrease in IRS1 levels in the skeletal muscle.

Conclusions

Our results suggest a critical role for the lncRNA H19-HDAC6 axis in regulating IRS1 levels in the skeletal muscle during diabetes and therefore restoring normal H19 levels might hold a therapeutic potential for the management of aberrant skeletal muscle physiology during insulin resistance and type 2 diabetes.
Proteomic analysis of low- and high-grade human colon adenocarcinoma tissues and tissue-derived primary cell lines reveals unique biological functions of tumours and new protein biomarker candidates
Authors: Munro Matthew J. , Wickremesekera Susrutha K. , Tan Swee T. , Peng Lifeng
Published: July 2022

Background

Colon cancer is the third most common cancer and second highest cause of cancer deaths worldwide. The aim of the study was to find new biomarkers for diagnosis, prognosis and therapeutic drug targets for this disease.

Methods

Four low-grade and four high-grade human colon adenocarcinoma tumours with patient-matched normal colon tissues were analysed. Additionally, tissue-derived primary cell lines were established from each tumour tissue. The cell lines were validated using DNA sequencing to confirm that they are a suitable in vitro model for colon adenocarcinoma based on conserved gene mutations. Label-free quantitation proteomics was performed to compare the proteomes of colon adenocarcinoma samples to normal colon samples, and of colon adenocarcinoma tissues to tissue-derived cell lines to find significantly differentially abundant proteins. The functions enriched within the differentially expressed proteins were assessed using STRING. Proteomics data was validated by Western blotting.

Results

A total of 4767 proteins were identified across all tissues, and 4711 across primary tissue-derived cell lines. Of these, 3302 proteins were detected in both the tissues and the cell lines. On average, primary cell lines shared about 70% of proteins with their parent tissue, and they retained mutations to key colon adenocarcinoma-related genes and did not diverge far genetically from their parent tissues. Colon adenocarcinoma tissues displayed upregulation of RNA processing, steroid biosynthesis and detoxification, and downregulation of cytoskeletal organisation and loss of normal muscle function. Tissue-derived cell lines exhibited increased interferon-gamma signalling and aberrant ferroptosis. Overall, 318 proteins were significantly up-regulated and 362 proteins significantly down-regulated by comparisons of high-grade with low-grade tumours and low-grade tumour with normal colon tissues from both sample types.

Conclusions

The differences exhibited between tissues and cell lines highlight the additional information that can be obtained from patient-derived primary cell lines. DNA sequencing and proteomics confirmed that these cell lines can be considered suitable in vitro models of the parent tumours. Various potential biomarkers for colon adenocarcinoma initiation and progression and drug targets were identified and discussed, including seven novel markers: ACSL4, ANK2, AMER3, EXOSC1, EXOSC6, GCLM, and TFRC.
Proteomics-based diagnostic peptide discovery for severe fever with thrombocytopenia syndrome virus in patients
Authors: Lee Sang-Yeop , Lee Hayoung , Yun Sung Ho , Park Edmond Changkyun , Seo Giwan , Kim Hye-Yeon , Jun Sangmi , Kim Nam Hoon , Tark Dongseob , Lee Ju Yeon , Lee Chang-Seop , Kim Seung Il
Published: July 2022

Background

Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging infectious virus which causes severe hemorrhage, thrombocytopenia, and leukopenia, with a high fatality rate. Since there is no approved therapeutics or vaccines for SFTS, early diagnosis is essential to manage this infectious disease.

Methods

Here, we tried to detect SFTS virus in serum samples from SFTS patients by proteomic analysis. Firstly, in order to obtain the reference MS/MS spectral data of SFTS virus, medium from infected Vero cell culture was used for shotgun proteomic analysis. Then, tryptic peptides in sera from SFTS patients were confirmed by comparative analysis with the reference MS/MS spectral data of SFTS virus.

Results

Proteomic analysis of culture medium successfully discovered tryptic peptides from all the five antigen proteins of SFTS virus. The comparative spectral analysis of sera of SFTS patients revealed that the N-terminal tryptic peptide of the nucleocapsid (N) protein is the major epitope of SFTS virus detected in the patient samples. The prevalence of the peptides was strongly correlated with the viral load in the clinical samples.

Conclusions

Proteomic analysis of SFTS patient samples revealed that nucleocapsid (N) protein is the major antigen proteins in sera of SFTS patients and N-terminal tryptic peptide of the N protein might be a useful proteomic target for direct detection of SFTS virus. These findings suggest that proteomic analysis could be an alternative tool for detection of pathogens in clinical samples and diagnosis of infectious diseases.
Vitamin C attenuates predisposition to high-fat diet-induced metabolic dysregulation in GLUT10-deficient mouse model
Authors: Jiang Chung-Lin , Tsao Chang-Yu , Lee Yi-Ching
Published: July 2022

Background

The development of type 2 diabetes mellitus (T2DM) is highly influenced by complex interactions between genetic and environmental (dietary and lifestyle) factors. While vitamin C (ascorbic acid, AA) has been suggested as a complementary nutritional treatment for T2DM, evidence for the significance and beneficial effects of AA in T2DM is thus far inconclusive. We suspect that clinical studies on the topic might need to account for combination of genetic and dietary factors that could influence AA effects on metabolism. In this study, we tested this general idea using a mouse model with genetic predisposition to diet-induced metabolic dysfunction. In particular, we utilized mice carrying a human orthologous GLUT10G128E variant (GLUT10G128E mice), which are highly sensitive to high-fat diet (HFD)-induced metabolic dysregulation. The genetic variant has high relevance to human populations, as genetic polymorphisms in glucose transporter 10 (GLUT10) are associated with a T2DM intermediate phenotype in nondiabetic population.

Results

We investigated the impacts of AA supplementation on metabolism in wild-type (WT) mice and GLUT10G128E mice fed with a normal diet or HFD. Overall, the beneficial effects of AA on metabolism were greater in HFD-fed GLUT10G128E mice than in HFD-fed WT mice. At early postnatal stages, AA improved the development of compromised epididymal white adipose tissue (eWAT) in GLUT10G128E mice. In adult animals, AA supplementation attenuated the predisposition of GLUT10G128E mice to HFD-triggered eWAT inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic dysregulation, and body weight gain, as compared with WT mice.

Conclusions

Taken together, our findings suggest that AA has greater beneficial effects on metabolism in HFD-fed GLUT10G128E mice than HFD-fed WT mice. As such, AA plays an important role in supporting eWAT development and attenuating HFD-induced metabolic dysregulation in GLUT10G128E mice. Our results suggest that proper WAT development is essential for metabolic regulation later in life. Furthermore, when considering the usage of AA as a complementary nutrition for prevention and treatment of T2DM, individual differences in genetics and dietary patterns should be taken into account.
Whole-Genome Sequencing of Rice Mutant Library Members Induced by N-Methyl-N-Nitrosourea Mutagenesis of Fertilized Egg Cells
Authors: Kubo Takahiko , Yamagata Yoshiyuki , Matsusaka Hiroaki , Toyoda Atsushi , Sato Yutaka , Kumamaru Toshihiro
Published: July 2022

Although targeted genome editing technology has become a powerful reverse genetic approach for accelerating functional genomics, conventional mutant libraries induced by chemical mutagens remain valuable for plant studies. Plants containing chemically induced mutations are simple yet effective genetic tools that can be grown without regard for biosafety issues. Whole-genome sequencing of mutant individuals reduces the effort required for mutant screening, thereby increasing their utility. In this study, we sequenced members of a mutant library of Oryza sativa cv. Nipponbare derived from treating single fertilized egg cells with N-methyl-N-nitrosourea (MNU). By whole-genome sequencing 266 M1 plants in this mutant library, we identified a total of 0.66 million induced point mutations. This result represented one mutation in every 146-kb of genome sequence in the 373 Mb assembled rice genome. These point mutations were uniformly distributed throughout the rice genome, and over 70,000 point mutations were located within coding sequences. Although this mutant library was a small population, nonsynonymous mutations were found in nearly 61% of all annotated rice genes, and 8.6% (3248 genes) had point mutations with large effects on gene function, such as gaining a stop codon or losing a start codon. WGS showed MNU-mutagenesis using rice fertilized egg cells induces mutations efficiently and is suitable for constructing mutant libraries for an in silico mutant screening system. Expanding this mutant library and its database will provide a useful in silico screening tool that facilitates functional genomics studies with a special emphasis on rice.