bluuebunny/crossref_metadata_2025 huggingface dataset:
“Blacks Can’t Jump”: The Racialization of Transit Police Responses to Fare Evasion
Authors: Carter TaLisa J. , Johnson Lallen T.
Published: April 2021

This study demonstrates that racially disparate fare evasion citation outcomes are the product of racialized social systems that allow transit police officers to determine the belongingness of Black riders in systems of mass transit. Using citation data from the Washington Metropolitan Area Transit Authority, we test the impact of race and place attributes on transit officer decisions to allocate punishment for subway fare evasion using mixed effects logistic regression controlling for individual and contextual predictors. Although rider racial identity alone proves statistically irrelevant, Black riders suspected of fare evasion possess an elevated risk for being fined as opposed to merely being warned at stations located within predominately white neighborhoods and as stations increase in ridership. These findings demonstrate how transit police officer discretion challenges Black belongingness on systems of public transportation. Broader implications of this work include the importance of scholarship linking statistical disparities to organizational intent and integrating diverse voices in policing policy development.
Preservation of the Tibial Stump During Anterior Cruciate Ligament Reconstruction Surgery Did Not Increase the Rate of Surgery for Symptomatic Cyclops Lesions
Authors: Webster Kate E. , Murgier Jerome , Feller Julian A. , Klemm Haydn J. , Devitt Brian M. , Whitehead Timothy S.
Published: April 2021

Background:

Preservation of the tibial stump during anterior cruciate ligament reconstruction (ACLR) is controversial. While proposed benefits include enhanced graft revascularization, improved proprioception, and decreased graft rupture rates, a potential complication is the development of a symptomatic cyclops lesion. It is therefore important to determine whether any benefits outweigh potential complications.

Purpose:

To determine whether greater preservation of the tibial stump remnant would be associated with a decreased graft rupture rate without a concomitant increase in the rate of surgery for symptomatic cyclops lesions at 2 years after ACLR.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A cohort of 658 patients in whom the amount of tibial stump preserved was classified as no stump (n = 228), <50% (n = 342), or >50% (n = 88) was followed up for 2 years, with graft ruptures and surgical treatment for cyclops lesions recorded. Contingency and Kaplan-Meier survival analyses were used to determine trends among the 3 remnant preservation groups in terms of graft rupture rates and surgery for cyclops lesions. Subgroup analysis was also conducted to examine sex-based differences.

Results:

There was no significant association between graft rupture rates and remnant preservation. There was a significant trend for fewer operations for symptomatic cyclops lesions with greater remnant preservation when the entire cohort was analyzed ( P = .04) and also when only female patients were analyzed ( P = .04).

Conclusion:

Although preservation of the tibial stump remnant was not associated with a reduced graft rupture rate, it was also not associated with increased rates of surgery for symptomatic cyclops lesions.
Pulmonary Hypertension as a Complication of Pediatric Cancer
Authors: Kirkpatrick Edward C.
Published: April 2021

Pediatric cancer is a life threatening disease known to create multi-organ complications that further compromise medical management affecting patient morbidity and mortality. Pulmonary hypertension (PH) is becoming more recognized as a complication of cancer and its therapies but has not been well characterized in pediatrics. Cancer pathophysiology can be uniquely set up to promote pulmonary vascular injury and remodeling that is similar to PH patients without cancer. This highlights the need to evaluate for PH clinically and with routine testing such as echocardiography during the course of a patient’s care even into adulthood. This review article will discuss the direct, indirect and therapy related aspects of cancer which can promote PH in these patients. This understanding is essential to target effective treatment options in a potentially fatal complication. Diagnostic and treatment algorithms are presented in relation to the most recent pediatric PH management guidelines.
The Impact of the COVID-19 Pandemic on Self-Reported Management of Chronic Conditions
Authors: Imeri Hyllore , Holmes Erin , Desselle Shane , Rosenthal Meagen , Barnard Marie
Published: April 2021

Chronic conditions (CCs) management during the COVID-19 pandemic and the impact of the pandemic on patient activation (PA) and health locus of control (HLOC) remain unknown. This cross-sectional online survey study examined the role of COVID-19 pandemic-related worry or fear in PA and HLOC among patients with CCs. Individuals with CCs (n = 300) were recruited through MTurk Amazon. The questionnaire included sociodemographic questions, the Patient Activation Measure, and the Multidimensional Health Locus of Control–Form B. Out of the 300 participants, 9.7% were diagnosed with COVID-19, and 7.3% were hospitalized. Patients with cancer, chronic kidney disease, chronic obstructive pulmonary disease, drug abuse/substance abuse, and stroke reported significant difficulties in managing their CCs due to worry or fear because of COVID-19. More than half of the sample (45.7%) reported COVID-19-related worry or fear about managing their CCs, and these patients had lower PA and lower external HLOC compared to patients not affected by COVID-19-related worry or fear. Health professionals should provide more support for patients facing difficulties in managing their CCs during the COVID-19 pandemic.
Civic Participation and Social Embeddedness: Differences Between Urban and Rural Communities
Authors: Kleiner Tuuli-Marja
Published: April 2021

Does civic participation lead to a large social network? This study claims that high levels of civic participation may obstruct individual social embeddedness. Using survey data from the German Survey on Volunteering (Deutscher Freiwilligensurvey; 1999–2009), this study conducts macro- as well as multi-level regressions to examine the link between civic participation and social embeddedness. Findings reveal that civic participation on the sub-national regional level is not generally associated with social embeddedness, but it affects the participants’ and non-participants’ possibilities for friendships differently. This holds especially true in urban areas, but the effect cannot be found in rural areas. The analysis has implications for further research to enhance the social embeddedness of the excluded.
Plasmin-mediated cleavage of high-molecular-weight kininogen contributes to acetaminophen-induced acute liver failure
Authors: Henderson Michael W. , Sparkenbaugh Erica M. , Wang Shaobin , Ilich Anton , Noubouossie Denis F. , Mailer Reiner , Renné Thomas , Flick Matthew J. , Luyendyk James P. , Chen Zu-Lin , Strickland Sidney , Stravitz R. Todd , McCrae Keith R. , Key Nigel S. , Pawlinski Rafal
Published: April 2021

Acetaminophen (APAP)-induced liver injury is associated with activation of coagulation and fibrinolysis. In mice, both tissue factor–dependent thrombin generation and plasmin activity have been shown to promote liver injury after APAP overdose. However, the contribution of the contact and intrinsic coagulation pathways has not been investigated in this model. Mice deficient in individual factors of the contact (factor XII [FXII] and prekallikrein) or intrinsic coagulation (FXI) pathway were administered a hepatotoxic dose of 400 mg/kg of APAP. Neither FXII, FXI, nor prekallikrein deficiency mitigated coagulation activation or hepatocellular injury. Interestingly, despite the lack of significant changes to APAP-induced coagulation activation, markers of liver injury and inflammation were significantly reduced in APAP-challenged high-molecular-weight kininogen-deficient (HK−/−) mice. Protective effects of HK deficiency were not reproduced by inhibition of bradykinin-mediated signaling, whereas reconstitution of circulating levels of HK in HK−/− mice restored hepatotoxicity. Fibrinolysis activation was observed in mice after APAP administration. Western blotting, enzyme-linked immunosorbent assay, and mass spectrometry analysis showed that plasmin efficiently cleaves HK into multiple fragments in buffer or plasma. Importantly, plasminogen deficiency attenuated APAP-induced liver injury and prevented HK cleavage in the injured liver. Finally, enhanced plasmin generation and HK cleavage, in the absence of contact pathway activation, were observed in plasma of patients with acute liver failure due to APAP overdose. In summary, extrinsic but not intrinsic pathway activation drives the thromboinflammatory pathology associated with APAP-induced liver injury in mice. Furthermore, plasmin-mediated cleavage of HK contributes to hepatotoxicity in APAP-challenged mice independently of thrombin generation or bradykinin signaling.
Requirement for antiapoptotic MCL-1 during early erythropoiesis
Authors: Turnis Meghan E. , Kaminska Ewa , Smith Kaitlyn H. , Kartchner Brittany J. , Vogel Peter , Laxton Jonathan D. , Ashmun Richard A. , Ney Paul A. , Opferman Joseph T.
Published: April 2021

Although BCL-xL is critical to the survival of mature erythrocytes, it is still unclear whether other antiapoptotic molecules mediate survival during earlier stages of erythropoiesis. Here, we demonstrate that erythroid-specific Mcl1 deletion results in embryonic lethality beyond embryonic day 13.5 as a result of severe anemia caused by a lack of mature red blood cells (RBCs). Mcl1-deleted embryos exhibit stunted growth, ischemic necrosis, and decreased RBCs in the blood. Furthermore, we demonstrate that MCL-1 is only required during early definitive erythropoiesis; during later stages, developing erythrocytes become MCL-1 independent and upregulate the expression of BCL-xL. Functionally, MCL-1 relies upon its ability to prevent apoptosis to promote erythroid development because codeletion of the proapoptotic effectors Bax and Bak can overcome the requirement for MCL-1 expression. Furthermore, ectopic expression of human BCL2 in erythroid progenitors can compensate for Mcl1 deletion, indicating redundancy between these 2 antiapoptotic family members. These data clearly demonstrate a requirement for MCL-1 in promoting survival of early erythroid progenitors.
Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results
Authors: Advani Ranjana H. , Moskowitz Alison J. , Bartlett Nancy L. , Vose Julie M. , Ramchandren Radhakrishnan , Feldman Tatyana A. , LaCasce Ann S. , Christian Beth A. , Ansell Stephen M. , Moskowitz Craig H. , Brown Lisa , Zhang Chiyu , Taft David , Ansari Sahar , Sacchi Mariana , Ho Linda , Herrera Alex F.
Published: April 2021

This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.
Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results
Authors: Roussel Murielle , Lauwers-Cances Valerie , Wuilleme Soraya , Belhadj Karim , Manier Salomon , Garderet Laurent , Escoffre-Barbe Martine , Mariette Clara , Benboubker Lotfi , Caillot Denis , Sonntag Cécile , Touzeau Cyrille , Dupuis Jehan , Moreau Philippe , Leleu Xavier , Facon Thierry , Hébraud Benjamin , Corre Jill , Attal Michel
Published: April 2021

Bortezomib, lenalidomide, and dexamethasone plus transplant is a standard of care for eligible patients with multiple myeloma. Because responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase 2 study, patients received eight 28-day cycles of carfilzomib (K) 20/36 mg/m2 (days 1-2, 8-9, 15-16), lenalidomide (R) 25 mg (days 1–21), and dexamethasone (d) 20 mg (days 1-2, 8-9, 15-16, 22-23). All patients proceeded to transplant after 4 cycles and received 1 year of lenalidomide maintenance (10 mg, days 1-21). The primary objective was stringent complete response at the completion of consolidation. Overall, 48 patients were screened and 46 enrolled; 21% had adverse cytogenetics. Among 42 evaluable patients after consolidation, 26 were in stringent complete response (CR; 61.9%), 27 were at least in CR (64.3%): 92.6% had undetectable minimal residual disease according to flow cytometry (≥2.5 × 10−5) and 63.0% according to next-generation sequencing (10−6). Median time to CR was 10.6 months. According to multiparametric flow cytometry and next-generation sequencing, 69.0% and 66.7% of patients, respectively, had undetectable minimal residual disease at some point. With a median follow-up of 60.5 months, 21 patients progressed, and 10 died (7 of multiple myeloma). Median progression-free survival was 56.4 months. There were no KRd-related deaths. Four patients discontinued the program due to toxicities; 56 serious adverse events were reported in 31 patients, including 8 cardiovascular events (2 heart failures, 5 pulmonary embolisms or deep vein thrombosis). Common grade 3/4 adverse events were hematologic (74%) and infectious (22%). In summary, 8 cycles of KRd produce fast and deep responses in transplant-eligible patients with newly diagnosed multiple myeloma. The safety profile is acceptable, but cardiovascular adverse events should be closely monitored. This clinical trial is registered at www.clinicaltrials.gov as #NCT02405364.
How do colorectal cancer patients rate their GP: a mixed methods study
Authors: Blackmore Tania , Chepulis Lynne , Keenan Rawiri , Kidd Jacquie , Stokes Tim , Weller David , Emery Jon , Lawrenson Ross
Published: April 2021

Background

New Zealand (NZ) has a high incidence of colorectal cancer (CRC) and low rates of early diagnosis. With screening not yet nationwide, the majority of CRC is diagnosed through general practice. A good patient-general practitioner (GP) relationship can facilitate prompt diagnosis, but when there is a breakdown in this relationship, delays can occur. Delayed diagnosis of CRC in NZ receives a disproportionally high number of complaints directed against GPs, suggesting deficits in the patient-GP connection. We aimed to investigate patient-reported confidence and ratings of their GP following the diagnostic process.

Methods

This study is a mixed methods analysis of responses to a structured questionnaire and free text comments from patients newly diagnosed with CRC in the Midland region of NZ. A total of 195 patients responded to the structured questionnaire, and 113 patients provided additional free text comments. Descriptive statistics were used to describe the study population and chi square analysis determined the statistical significance of factors possibly linked to delay. Free text comments were analysed using a thematic framework.

Results

Most participants rated their GP as ‘Very good/Good’ at communication with patients about their health conditions and involving them in decisions about their care, and 6.7% of participants rated their overall level of confidence and trust in their GP as ‘Not at all’. Age, gender, ethnicity and a longer diagnostic interval were associated with lower confidence and trust. Free text comments were grouped in to three themes: 1. GP Interpersonal skills; (communication, listening, taking patient symptoms seriously), 2. Technical competence; (speed of referral, misdiagnoses, lack of physical examination), and 3. Organisation of general practice care; (appointment length, getting an appointment, continuity of care).

Conclusions

Māori, females, and younger participants were more likely to report low confidence and trust in their GP. Participants associate a poor diagnostic experience with deficits in the interpersonal and technical skills of their GP, and health system factors within general practice. Short appointment times, access to appointments and poor GP continuity are important components of how patients assess their experience and are particularly important to ensure equal access for Māori patients.
Clinical and CT features of mild-to-moderate COVID-19 cases after two sequential negative nucleic acid testing results: a retrospective analysis
Authors: Rong Yan , Wang Fei , Tian Jinfei , Liang Xinhua , Wang Jing , Li Xiaoli , Zhang Dandan , Liu Jing , Zeng Huadong , Zhou Yang , Shi Yi
Published: April 2021

Background

The clinical and imaging features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections that progressed to coronavirus disease 2019 (COVID-19) have been explored in numerous studies. However, little is known about these features in patients who received negative respiratory nucleic acid test results after the infections resolved. In this study, we aim to describe these features in a group of Chinese patients.

Methods

This retrospective study includes 51 patients with mild-to-moderate COVID-19 (median age: 34.0 years and 47.1% male) between January 31 and February 28, 2020. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were collected before and after two consecutive negative respiratory SARS-CoV-2 tests.

Results

Following a negative test result, the patients’ clinical symptoms continued to recover, but abnormal imaging findings were observed in all moderate cases. Specifically, 77.4% of patients with moderate COVID-19 exhibited multi-lobar lung involvement and lesions were more frequently observed in the lower lobes. The most common CT imaging manifestations were ground-glass opacities (51.6%) and fibrous stripes (54.8%%). Twelve of the 31 patients with moderate COVID-19 underwent repeated chest CT scans after a negative SARS-CoV-2 test. Among them, the ground-glass opacities decreased by > 60% within 1 week in seven patients (58.3%), but by < 5% in four patients (13.8%).

Conclusions

Following a positive and subsequent negative SARS-CoV-2 tests, patients with COVID-19 continued to recover despite exhibiting persistent clinical symptoms and abnormal imaging findings.
MPT64 assays for the rapid detection of Mycobacterium tuberculosis
Authors: Cao Xun-Jie , Li Ya-Ping , Wang Jia-Ying , Zhou Jie , Guo Xu-Guang
Published: April 2021

Background

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB). An estimated 1.7 billion people worldwide are infected with Mycobacterium tuberculosis (LTBI) during the incubation period without any obvious symptoms. Because of MTB’s high infection and mortality rates, there is an urgent need to develop a fast, portable, and sensitive diagnostic technology for its detection.

Methods

We included research from PubMed, Cochrane Library, Web of Science, and Embase and extracted the data. MetaDisc and STATA were used to build forest plots, Deek’s funnel plot, Fagan plot, and bivariate boxplot for analysis.

Results

Forty-six articles were analyzed, the results of which are as follows: sensitivity and specificity were 0.92 (0.91–0.93) and 0.95 (0.94–0.95) respectively. The NLR and PLR were 0.04 (95% CI 0.03–0.07) and 25.32 (95% CI 12.38–51.78) respectively. DOR was 639.60 (243.04–1683.18). The area under the SROC curve (AUC) was 0.99.

Conclusions

MPT64 exhibits good diagnostic efficiency for MTB. There is no obvious heterogeneity between the three commercial kits.
Maternal and fetal outcomes of patients with liver cirrhosis: a case-control study
Authors: Gao Xiang , Zhu Yunxia , Liu Haixia , Yu Hongwei , Wang Ming
Published: April 2021

Background

We aimed to describe the characteristics and outcomes in pregnant women with liver cirrhosis, and identify the predictors of adverse events of mother and fetus.

Methods

Retrospectively collected mothers with liver cirrhosis in our center from 6/2010 to 6/2019. Women without liver cirrhosis were selected as a control in a 1:2 ratio. The primary assessment was the frequency of maternal and fetal adverse events. The secondary assessment was the adverse events in patients continuing pregnancy or not and the factors to predict the severe adverse events.

Results

Of 126 pregnancies enrolled, 29 pregnancies were terminated for worrying disease progression and 97 pregnancies continued. One hundred ninety-four pregnancies without liver cirrhosis were selected as control. At baseline, patients with liver cirrhosis have a lower level of platelet, hemoglobin, prothrombin activity, and a higher level of ALT, total Bilirubin, creatinine. Compared to control, patients with liver cirrhosis had a higher frequency of adverse events, including bleeding gums (7.2%vs. 1.0%), TBA elevation (18.6%vs.3.1%), infection (10.3%vs.0.5%), cesarean section (73.6%vs.49.5%), postpartum hemorrhage (13.8% vs 2.1%), blood transfusion (28.9% vs 2.1%), new ascites or aggravating ascites (6.2% vs.0%), MODS (7.2% vs.0.5%) and intensive care unit admissions (24.1% vs 1.1%). The incidence of severe maternal adverse events was also higher (32.0% vs 1.5%). Women who chose to terminated the pregnancy had less severe adverse events (3.4% vs.32.0%).

A higher frequency of fetal/infants’ complications was observed in liver cirrhosis population than control, including newborn asphyxia (10.2% vs1.1%), low birth weight infant (13.6% vs. 2.6%). In patients who progressed into the third trimester, multivariable regression analysis demonstrated that severe adverse events were associated with a higher CTP score (OR 2.128, 95% CI [1.002, 4.521], p = 0.049). Wilson’s disease related liver cirrhosis has a better prognosis (OR = 0.009, 95% CI [0, 0.763], p = 0.038).

Conclusions

The incidence of the adverse events was significantly increased in pregnancies complicated by cirrhosis. The predictor of severe adverse events is higher CTP score. Wilson’s disease induced liver cirrhosis have a better prognosis. Timely termination of pregnancy during the first trimester may avoid the incidence of severe adverse events.
Public health practitioner perspectives on dealing with measles outbreaks if high anti-vaccination sentiment is present
Authors: Robinson Penelope , Wiley Kerrie , Degeling Chris
Published: April 2021

Background

Communities with low vaccination rates are at greater risk during outbreaks of vaccine preventable diseases. Most Australian parents support vaccines, but some refuse and are often judged harshly by their community, especially during an outbreak. We sought the perspectives of Australian public health experts on the key issues faced when managing a measles outbreak in an area with high anti-vaccination sentiment.

Methods

A measles outbreak scenario formed the basis of a 3-round modified Delphi process to identify key practitioner concerns in relation to parents/carers who don’t follow the recommended vaccination schedule. We surveyed a range of professionals in the field: policymakers, infectious disease experts, immunisation program staff, and others involved in delivering childhood vaccinations, to identify key priorities when responding to an outbreak in a community with low vaccination coverage.

Results

Findings indicate that responses to measles outbreaks in communities with high anti-vaccination sentiment are motivated by concerns about the potential for a much larger outbreak event. The highest operational priority is to isolate infected children. The two most highly ranked practical issues are mistrust from non-vaccinating members of the local region and combatting misinformation about vaccines. Trying to change minds of such individuals is not a priority during an outbreak, nor is vaccinating their children. Using media and social media to provide information about the outbreak and measures the public can take to limit the spread of the disease was a focus.

Conclusions

Our findings provide a deeper understanding of the challenges faced during an outbreak and priorities for communicating with communities where there is a high level of anti-vaccination sentiment. In the context of a global pandemic, the results of this study also have implications for managing public health responses to community transmission of SARS-CoV-2, as COVID-19 vaccines becomes widely available.
Association between distress and displacement settings: a cross-sectional survey among displaced Yazidis in northern Iraq
Authors: Pham Phuong N. , Fozouni Laila , al-Saiedi Abdulrazzaq , Coughlin Kevin , Vinck Patrick
Published: April 2021

Background

Globally 70.8 million people have been forcibly displaced from their homes and are at disproportionally high risk for trauma. At the time of this study, there was an estimated 1.6 million internally displaced persons (IDP) in Iraq, more than two-thirds of whom reside in private, urban settings. This study aims to understand the impact of post-displacement accommodation on mental well-being of the Yazidi minority group displaced in Iraq.

Methods

Multi-stage stratified sampling was used to randomly select IDPs in camp and out of camp settlements in northern Iraq. Standardized questionnaires evaluated factors including exposure to violence and self-reported distress symptoms (measured by Impact of Event Scale-Revised). A multi-variate linear model assessed the relationship between settlement setting and distress symptoms.

Results

One thousand two hundred fifty-six displaced Yazidi participants were included in the study: 63% in camps and 37% out of camps. After controlling for exposure to violence, social cohesion, unemployment, and access to basic services, IDPs in camps were predicted to have a 19% higher mean distress symptom score compared to those out of camps.

Conclusions

This study provides a framework to investigate post-displacement accommodation as a potential intervention to improve well-being for displaced populations. With a shift towards new models of emergency and long-term housing, it is important to understand the potential and limitations of more decentralized models, and identify effective methods to maintain access to basic services while improving living conditions for both displaced populations and their host communities.
The burden of illness in initiating intermittent catheterization: an analysis of German health care claims data
Authors: Angermund Almuth , Inglese Gary , Goldstine Jimena , Iserloh Laura , Libutzki Berit
Published: April 2021

Background

Intermittent catheterization (IC) is a common medical technique to drain urine from the bladder when this is no longer possible by natural means. The objective of this study was to evaluate the standard of care and the burden of illness in German individuals who perform intermittent catheterization and obtain recommendations for improvement of care.

Methods

A descriptive study with a retrospective, longitudinal cohort design was conducted using the InGef research database from the German statutory health insurance claims data system. The study consisted of individuals with initial IC use in 2013–2015.

Results

Within 3 years 1100 individuals with initial IC were identified in the database (~ 19,000 in the German population). The most common IC indications were urologic diseases, spinal cord injury, Multiple Sclerosis and Spina Bifida. Urinary tract infections (UTI) were the most frequent complication occurring 1 year before index (61%) and in follow-up (year 1 60%; year 2 50%). Resource use in pre-index including hospitalizations (65%), length of stay (12.8 ± 20.0 days), physician visits (general practitioner: 15.2 ± 29.1), prescriptions of antibiotics (71%) and healthcare costs (€17,950) were high. Comorbidities, complications, and healthcare resource use were highest 1 year before index, decreasing from first to second year after index.

Conclusions

The data demonstrated that prior to initial catheterization, IC users experienced UTIs and high healthcare utilization. While this demonstrates a potential high burden of illness prior to initial IC, UTIs also decreased over time, suggesting that IC use may have a positive influence. The findings also showed that after the first year of initial catheterization the cost decreased. Further studies are needed to better understand the extent of the burden for IC users compared to non-IC users.
Primary care physicians’ knowledge, attitudes and concerns about bariatric surgery and the association with referral patterns: a Swedish survey study
Authors: Memarian Ensieh , Carrasco Daniel , Thulesius Hans , Calling Susanna
Published: April 2021

Background

Obesity prevalence is increasing globally. Bariatric surgery is an effective treatment for severe and complex obesity resulting in significant and sustained weight loss. In Sweden, most bariatric surgery patients are referred by primary care physicians. We aimed to explore barriers for physicians to refer patients with severe and complex obesity for bariatric surgery.

Methods

A questionnaire survey was in 2019 emailed to 1100 primary care physicians in the Skåne and Kronoberg regions in south Sweden. The survey focused on referral patterns, knowledge and attitudes towards bariatric surgery and concerns about postoperative complications. We created different statistical indices for referral patterns, knowledge, attitudes and concerns about bariatric surgery. To analyze the correlation between these indices, we did Spearman’s correlations and regression analyses.

Results

Of 1100 email respondents, we received 157 (14%) completed surveys. Among 157 physician respondents, 73% answered that they had good knowledge about the referral criteria for bariatric surgery, whereas 55 and 60% answered correctly to two items on criteria for bariatric surgery. A majority of respondents (84%) stated that their patients initiated referral to bariatric surgery. Half of the respondents had concerns about postoperative medical and surgical complications, but another half had a positive attitude to bariatric surgery as a treatment for obesity comorbidities. Almost half of the respondents (44%) answered that they needed to learn more about bariatric surgery.

We found significant positive correlations between high knowledge and referral patterns (r = 0.292, p < 0.001) and positive attitudes (r = 0.235, p < 0.001) respectively. We found significant reverse correlations between concerns and referral patterns (r = − 0.355, p < 0.001) and between positive attitudes and concerns (r = − 0.294, p < 0.001). In logistic regression high levels of concerns explained low willingness to refer for bariatric surgery (Odds Ratio 0.2, 95% confidence interval 0.1–0.7).

Conclusion

According to this Swedish survey among primary care physicians, high levels of concerns about bariatric surgery among physicians seemed to be a barrier to refer patients with severe and complex obesity for bariatric surgery. Since high knowledge about obesity and bariatric surgery correlated negatively to concerns and positively to favorable attitudes to bariatric surgery, more knowledge about obesity and bariatric surgery is warranted.
‘Making of a Strong Woman’: a constructivist grounded theory of the experiences of young women around menarche in Papua New Guinea
Authors: Maulingin-Gumbaketi Elizabeth , Larkins Sarah , Gunnarsson Ronny , Rembeck Gun , Whittaker Maxine , Redman-MacLaren Michelle
Published: April 2021

Background

Menarche, the first menstruation, is a significant developmental milestone for females. In Papua New Guinea (PNG), menarche is an important socio-cultural event marking transition from girlhood to womanhood. PNG is a culturally and linguistically diverse nation, with wide-ranging socio-cultural beliefs and practices around menarche. This study explored post-menarcheal women’s understanding about body changes and menarche, preparation for menarche, and related cultural beliefs and practices at menarche.

Methods

A constructivist grounded theory study was conducted with 98 female participants who originated from four PNG provinces: Eastern Highlands Province; East Sepik Province; Milne Bay Province; and National Capital District. The participants were purposively and theoretically sampled, with 10 focus group discussions and six individual interviews conducted using a semi-structured interview guide for data collection. Focus group discussions and interviews were voice recorded and transcribed. Data were inductively analyzed using initial, intermediate and advanced coding, memos and constant comparative methods to develop a theoretical model that explains women’s experiences at menarche. Interview participants also identified actions required to improve future experiences of girls at menarche in PNG.

Results

A grounded theory comprising the core category of ‘Making of a Strong Woman’ and four interconnecting categories (‘Having Baby Sense’; ‘Beginning of Learning’; ‘Intensifying Learning’; and ‘Achieving Womanhood’) was constructed. ‘Urban’ and ‘Rural’ represented both geographical and socio-cultural intervening conditions that influence the experiences of girls at menarche. Experiences of young women at menarche were rooted in socio-cultural beliefs and practices. Women reported being physically and emotionally distressed and unprepared at onset of menarche. Mothers were considered important support, however, their ability to adequately prepare their daughters is limited by shame and secrecy. Despite these limitations, cultural practices at menarche provided an opportunity for intensive preparation of girls for womanhood.

Conclusion

Limited pre-menarcheal awareness of the meaning of body changes and menarche of girls was linked to culture of shame and secrecy about open discussion on sexuality. However, traditional cultural practices provide an opportunity for collective support and focused learning for girls. Findings from this study have implications for broader sexual and reproductive health education programs in addressing menstrual health and hygiene in PNG, and the Pacific.
The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Authors: Que Tengcheng , Wang Huifeng , Yang Weifei , Wu Jianbao , Hou Chenyang , Pei Surui , Wu Qunying , Li Liu Ming , Wei Shilu , Xie Xing , Huang Hongli , Chen Panyu , Huang Yiming , Wu Aiqiong , He Meihong , Nong Dengpan , Wei Xiao , Wu Junyi , Nong Ru , Huang Ning , Zhou Qingniao , Lin Yaowang , Lu Tingxi , Wei Yongjie , Li Shousheng , Yao Jianglong , Zhong Yanli , Qin Huayong , Tan Luohao , Li Yingjiao , Li Weidong , Liu Tao , Liu Sanyang , Yu Yongyi , Qiu Hong , Jiang Yonghua , Li Youcheng , Liu Zhijin , Huang Cheng Ming , Hu Yanling
Published: April 2021

Background

Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche.

Results

In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies.

Conclusions

These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.
Combating drug resistance in acute myeloid leukaemia by drug rotations: the effects of quizartinib and pexidartinib
Authors: Yang Jingmei , Lindström H. Jonathan G. , Friedman Ran
Published: April 2021

Background

Acute myeloid leukaemia (AML) is an aggressive blood cancer. In approximately 30% of the cases, driver mutations in the FLT3 gene are identified. FLT3 inhibitors are used in treatment of such patients together with cytotoxic drugs or (in refractory AML) as single agents. Unfortunately, resistance to FLT3 inhibitors limits their efficacy. Resistance is often due to secondary mutations in the gene encoding the molecular target. The gatekeeper mutation F691L confers resistance to specific FLT3 inhibitors such as quizartinib, but pexidartinib is much less resistance to this mutation. Pexidartinib alone is however sensitive to many other resistance mutations. In chronic myeloid leukaemia (CML), it has been suggested that rotation between drugs with a different landscape of resistance mutations might postpone the emergence of resistance.

Methods

We studied the effect of quizartinib and pexidartinib in AML cell lines that express FLT3 (MOLM-14 and MV4-11). Using a rotation protocol, we further examined whether the emergence of resistance could be postponed. Computational modelling was used to analyse the onset of resistance and suggest which mutations are most likely to occur in a quantitative fashion.

Results

The cells were sensitive to both inhibitors but quickly developed resistance that could be inherited, suggesting a genetic origin. Rotation protocols were not useful to postpone the emergence of resistance, which implies that such protocols, or changing from pexidartinib to quizartinib (or vice-versa) should not be used in patients. The computational modelling led to similar conclusions and suggested that F691L is the most common mutation to occur with quizartinib, and also when both drugs are used in rotation.

Conclusions

AML patients are not likely to benefit from a quizartinib/pexidartinib rotation protocol. A combination of tyrosine kinase inhibitors (with different molecular targets) might be more useful in the future. Development of specific FLT3 inhibitors that are less sensitive to resistance mutations might also lead to a better outcome.
FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway
Authors: Tuluhong Dilihumaer , Chen Tao , Wang Jingjie , Zeng Huijuan , Li Hanjun , Dunzhu Wangmu , Li Qiurong , Wang Shaohua
Published: April 2021

Background

Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism.

Methods

The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.

Results

FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.

Conclusion

FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.
Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin
Authors: Raffaele Marco , Kovacovicova Kristina , Frohlich Jan , Lo Re Oriana , Giallongo Sebastiano , Oben Jude A. , Faldyna Martin , Leva Lenka , Giannone Antonino Giulio , Cabibi Daniela , Vinciguerra Manlio
Published: April 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced β-gal-positive senescent cells in human HCC xenografted mice. Whether D + Q has an effect on the age-associated spectrum of NAFLD-inflammation-HCC remains unknown.

Methods

Here, we utilized an established model of age- and obesity-associated HCC, the low dose diethylnitrosamine (DEN)/high fat diet (HFD), a regimen promoting liver inflammation and tumorigenesis over a long period of 9 months. Four groups of mice each were created: group 1 included control untreated mice; group 2 included mice treated with D + Q; group 3 included mice undergoing the DEN/HFD protocol; group 4 included mice undergoing the DEN/HFD protocol with the administration of D + Q. At the end of the chemical/dietary regimen, we analyzed liver damage and cell senescence by histopathology, qPCR and immunoblotting approaches.

Results

Unexpectedly, D + Q worsened liver disease progression in the DEN/HFD mouse model, slightly increasing histological damage and tumorigenesis, while having no effect on senescent cells removal.

Conclusions

In summary, using an animal model that fully recapitulates NAFLD, we demonstrate that these compounds are ineffective against age-associated NAFLD-induced HCC.
Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma
Authors: Hou Ping , Su Xiaoyan , Cao Wei , Xu Liping , Zhang Rongguiyi , Huang Zhihao , Wang Jiakun , Li Lixiang , Wu Linquan , Liao Wenjun
Published: April 2021

Background

Primary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. The CRTC1-MAML2 fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature.

Methods

A 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Fluorescence in situ hybridization (FISH) was used to detect the CRTC1-MAML2 fusion gene in HMEC. Whole-exome sequencing and Sanger sequencing were used to reveal the molecular characteristics of HMEC and analysis was performed with public data. Pedigree investigation was performed to identify susceptibility genes.

Results

Hematoxylin–eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. The CRTC1-MAML2 fusion gene was not detected in the primary HMEC, and somatic mutations in GNAS, KMT2C and ELF3 genes were identified by sequencing. Analyses of public data revealed somatic GNAS alterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of Fanconi’s anemia susceptibility genes were present in the pedigree.

Conclusions

Here we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi’s anemia gene mutations and somatic GNAS R201H mutation.
Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis
Authors: Kakimoto Soichiro , Miyamoto Morikazu , Einama Takahiro , Takihata Yasuhiro , Matsuura Hiroko , Iwahashi Hideki , Ishibashi Hiroki , Sakamoto Takahiro , Hada Taira , Suminokura Jin , Ito Tsubasa , Suzuki Rie , Suzuki Ayako , Takano Masashi
Published: April 2021

Background

This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma.

Methods

Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined.

Results

Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p < 0.01). More patients with mesothelin expression showed myometrial invasion of more than 50% (p = 0.028) and positive lymphovascular invasion (p = 0.027). Similarly, more patients with co-expression of mesothelin and CA125 had myometrial invasion of more than 50% (p = 0.016) and positive lymphovascular invasion (p = 0.02). Patients with mesothelin expression and co-expression of mesothelin and CA125 demonstrated worse progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, mesothelin expression and co-expression were poor prognostic factors for PFS (mesothelin expression: hazard ratio [HR] = 2.14, p < 0.01; co-expression: HR = 2.19, p < 0.01) and OS (mesothelin expression: HR = 2.18, p < 0.01; co-expression: HR = 2.22, p < 0.01).

Conclusions

Mesothelin expression and co-expression might be associated with tumor aggressiveness and poor prognosis in patients with endometrial carcinoma. Persons with mesothelin-expressing endometrial cancers present a particularly high medical unmet need.