bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting Best Practices for Medical Science Liaisons Position Statement from the APPA, IFAPP, MAPS and MSLS
Authors: Theron Paul , Britland Matthew , Holder Donna , Ikeda Yasushi , Rewers Ralph F. , Tiku Ajay 
Published: July 2021

AbstractThis position paper is intended to provide recommendations that will help lay the foundation for best practices for medical science liaisons (MSLs) and their activities. Its objective is to outline the roles and responsibilities expected of an MSL and provide clarity on the juxtaposition of MSLs and Sales representatives (SRs) when it comes to scientific exchange versus promotional messaging. It is of utmost importance that industry integrity and ethical standards are assured during external stakeholder engagement as well as medical and scientific communications. This guidance, delivered through the lens of APPA, IFAPP, MAPS and the MSLS executive committees, has been prepared primarily as a supportive resource to assist the Medical Affairs teams in the industry to develop their own set of standard operating procedures (SOPs), codes of conduct and policies within the framework of relevant industry regulations. We acknowledge that whilst there are guidelines already available that provide excellent directive to the MSL function, this paper is a review and distillation of these existing recommendations combined with the perspectives of four peak professional bodies to offer a practically focused resource to help MSLs interact, collaborate and exchange scientific information appropriately with external experts when out in the field.
Differential Gene Expression in Post-Finasteride Syndrome Patients
Authors: Howell Skyler , Song Weitao , Pastuszak Alexander , Khera Mohit 
Published: July 2021

ABSTRACTBackgroundAn organic etiology underpinning post-finasteride syndrome, a constellation of persistent sexual, neuropsychiatric, and somatic symptoms reported by men exposed to 5-alpha-reductase inhibitors (5ARIs), is debated. Persistent changes in neurosteroid levels or androgen receptor expression have been implicated.AimTo determine whether differences in gene expression, especially in relevant biologic pathways, exist between patients reporting post-finasteride syndrome symptoms and healthy controls.MethodsThis was a single center, prospective case-control study taking place between March 2013 and September 2018. Men 18 years and older being evaluated for sexual dysfunction (study) or circumcision (control) were eligible for inclusion. Twenty-six men with a history of 5ARI use reporting symptoms consistent with post-finasteride syndrome were included in the patient group. Twenty-six men consented to inclusion in the control group.OutcomesThe primary outcome measure is gene expression data for genes affecting neurosteroid levels and androgen receptor activity from penile skin cells.RESULTSGene expression of cells from penile skin samples from twenty-six men of median age 38 years (IQR, 33-42) in the study group was compared with that from twenty-six men of median age 41 years (IQR, 35-62) in the control group (P = .13), with 1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients. Androgen receptor expression was significantly higher in study patients compared to controls (9.961 vs 9.494, adjusted P value = .01). Serum levels of androgen receptor activity markers 5α-androstanediol (0.950 ng/mL [0.749-1.587] vs 0.949 [0.817-1.337], P = .34) or 3α-androstanedione (3.1 ng/mL [1.925-5.475] vs 6.7 [3.375-11.4], P = .31) revealed no significant differences. No significant differences were found between the number of trinucleotide repeats (21.5 [20-23.75], 22 [19-25], P = .94).Clinical ImplicationsIn this study we present evidence of gene expression correlating with observed biologic differences in patients with post-finasteride syndrome; providers who prescribe 5ARIs should be aware and advise their patients accordingly.Strengths & LimitationsStrengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality.CONCLUSIONThis study is the first to consider and demonstrate gene expression differences in patients with PFS as a potential etiology of sexual dysfunction.
Mental Healthcare Utilization of Transgender Youth Before and After Affirming Treatment
Authors: Hisle-Gorman Elizabeth , Schvey Natasha A. , Adirim Terry A. , Rayne Anna K. , Susi Apryl , Roberts Timothy A. , Klein David A. 
Published: July 2021

ABSTRACTObjectiveTransgender and gender-diverse (TGD) adolescents experience increased mental health risk compared to cisgender peers. Limited research suggests improved outcomes following gender-affirmation. This study examined mental healthcare and psychotropic medication utilization among TGD youth compared to their siblings without gender-related diagnoses and explored utilization patterns following gender-affirming care.MethodThis retrospective cohort study used military healthcare data from 2010–2018 to identify mental healthcare diagnoses and visits, and psychotropic medication prescriptions among TGD youth who received care for gender dysphoria before age 18, and their siblings. Logistic and Poisson regression analyses compared mental health diagnosis, visits, and psychotropic prescriptions of TGD youth to their siblings, and compared healthcare utilization pre- and post-initiation of gender-affirming pharmaceuticals among TGD adolescents.RESULTS3,754 TGD adolescents and 6,603 cisgender siblings were included. TGD adolescents were more likely to have a mental health diagnosis (OR 5.45, 95% CI [4.77–6.24]), use more mental healthcare services (IRR 2.22; 95% CI [2.00–2.46]), and be prescribed more psychotropic medications (IRR = 2.57; 95% CI [2.36–2.80]) compared to siblings. The most pronounced increases in mental healthcare were for adjustment, anxiety, mood, personality, psychotic disorders, and suicidal ideation/attempted suicide. The most pronounced increased in psychotropic medication were in SNRIs, sleep medications, anti-psychotics and lithium. Among 963 TGD youth (Mage: 18.2) using gender-affirming pharmaceuticals, mental healthcare did not significantly change (IRR = 1.09, 95% CI [0.95–1.25]) and psychotropic medications increased (IRR = 1.67, 95% CI [1.46–1.91]) following gender-affirming pharmaceutical initiation; older age was associated with decreased care and prescriptions.CONCLUSIONResults support clinical mental health screening recommendations for TGD youth. Further research is needed to elucidate the longer-term impact of medical affirmation on mental health, including family and social factors associated with the persistence and discontinuation of mental healthcare needs among TGD youth.
Not only a listener: female frog-biting midges (Corethrellidae) also distinguish the shape of frogs
Authors: da Silva Fernando Rodrigues , Breviglieri Crasso Paulo Bosco 
Published: July 2021

AbstractIt is well known that female adults of frog-biting midges (Corethrellidae) are attracted by anuran mating calls. However, the role of host-emitted cues other than mating calls in determining the level of attraction remains poorly understood. Here, we performed field playback experiments to test how the host-seeking behaviour of Corethrella Coquillett is influenced by different sound stimuli: mating call of a tree frog, cricket call, and no sound. Then, after long-distance host detection, we evaluated if Corethrella can distinguish landing sites by using at short distance the colour and/or shape of anurans. For that, we placed artificial models of frogs with different colours (light green and dark brown) and an artificial caterpillar model (light green colour) on the top of speakers. We found that only frog mating calls presented with the visual cue of an artificial frog were attacked by Corethrella, suggesting that frog shape, regardless of colour, is an important cue for the identification of its hosts. This is the first study providing evidence that after flying long distances guided by frog calls, Corethrella can identify their hosts using visual cues at short distances.
Crosslinguistic perceptions of /s/ among English, French, and German listeners
Authors: Boyd Zac , Fruehwald Josef , Hall-Lew Lauren 
Published: July 2021

AbstractThis study reports the results of a crosslinguistic matched guise test examining /s/ and pitch variation in judgments of sexual orientation and nonnormative masculinity among English, French, and German listeners. Listeners responded to /s/ and pitch manipulations in native and other language stimuli (English, French, German, and Estonian). All listener groups rate higher pitch guises as more gay- and effeminate-sounding than lower pitch guises. However, only English listeners hear [s+] guises as more gay- and effeminate-sounding than [s] or [s−] guises for all stimuli languages. French and German listeners do not hear [s+] guises as more gay- or effeminate-sounding in any stimulus language, despite this feature's presence in native speech production. English listener results show evidence of indexical transfer, when indexical knowledge is applied to the perception of unknown languages. French and German listener results show how the enregistered status of /s/ variation affects perception, despite crosslinguistic similarities in production.
Ferroptosis Regulation by Nutrient Signalling
Authors: Qi Yingao , Zhang Xiaoli , Wu Zhihui , Tian Min , Chen Fang , Guan Wutai , Zhang Shihai 
Published: July 2021

AbstractTremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.
Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study
Authors: Gist Katja M. , Borasino Santiago , SooHoo Megan , Soranno Danielle E. , Mack Emily , Hock Kristal M. , Rahman A.K.M. Fazlur , Brinton John T. , Basu Rajit K. , Alten Jeffrey A. 
Published: July 2021

AbstractBackground:Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes.Methods:Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay.Results:One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004).Conclusions:Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.
Double-chambered right ventricle masquerading as bipartite right ventricle
Authors: Ahmed A. Shaheer , Agarwal Tushar 
Published: July 2021

AbstractA 10-day-old neonate with pulmonary consolidation was referred for echocardiography to rule out CHD. At first glance, the morphology appeared to be a bipartite right ventricle with normal tricuspid and pulmonary valves. In-depth analysis, however, of the images showed a double-chambered right ventricle, in which the inlet and outlet portions of the right ventricle were isolated from the apical component of the right ventricle, which itself communicated with the left ventricle through a ventricular septal defect. There was a normal pulmonary valve and tricuspid annulus.
Beta-blocker use after complete repair of tetralogy of Fallot: an analysis of a national database
Authors: Villarreal Enrique G. , Farias Juan S. , Tweddell James S. , Loomba Rohit S. , Flores Saul 
Published: July 2021

AbstractIntroduction:In patients with right ventricular diastolic dysfunction after complete repair of tetralogy of Fallot, some employ the use of beta-blockade. The theoretical benefit of this therapy is felt to be one of the two: 1) reduction in heart rate with subsequent increase in diastolic filling time and stroke volume; 2) halting or reversal of right ventricular remodelling. This study aimed to characterise the use of beta-blockade in paediatric admissions with complete repair of tetralogy of Fallot and characterise the effects of beta-blockade on admission characteristics.Methods:Admissions from 2004 to 2015 in the Pediatric Health Information System database with complete repair of tetralogy of Fallot were identified. Characteristics between admissions with and without beta-blockade were compared by univariate analysis. Next, regression analyses were conducted to determine the independent association of beta-blockade on length of admission, billed charges, cardiac arrest, and inpatient mortality while controlling for demographic variables and comorbidities.Results:A total of 3594 admissions were included in the final analyses. Of these, 371 employed beta-blockade. Admissions with beta-blockade were more likely to have heart failure and tachyarrhythmias. These admissions also tended to be longer by univariate analysis. Regression analyses demonstrated that beta-blockade was independently associated with a 2.8-day increase in length of stay and no statistically significant change in billed charges, cardiac arrest, or inpatient mortality.Conclusions:Beta-blockade after complete repair of tetralogy of Fallot is associated with a longer length of stay but did not statistically significantly impact billed charges, cardiac arrest, or inpatient mortality.
The value within multiform commodities: North African phosphates and global markets in the interwar period
Authors: Gruskin Rebecca 
Published: July 2021

AbstractPhosphates mined in France’s North African empire fed interwar Europe’s voracious appetite for chemical fertilizers. In critique of histories vesting commodities themselves with the agency to make the modern world, I trace not the substance but the value embedded within it. By following value, I argue that the ‘commodity’ is not a stable unit of analysis. Rather, commodities are multiform. They can acquire myriad properties when the value embedded within them changes across time and place. During the interwar period, phosphates’ character as a commodity transmuted in relation to flows of other goods, movements of labour, global financial exigencies and imperial considerations. As phosphates assumed new forms, the geographic scales over which they operated changed too. Through North African phosphates, I explore value-making processes that perpetuated capital-intensive farming, allowing for a history not of the commodity-as-substance but of the commodity-as-historical-object whose analytical boundaries and forms shifted across contexts.
A Pareto Multi‐Objective Optimization Approach for Anisotropic Shale Models
Authors: Zidan A. , Li Y. E. , Cheng A. 
Published: July 2021

AbstractWhen the elastic parameters of rocks such as shales vary with the propagation direction of a passing seismic wave that rock is called anisotropic. Modern seismic data are typically acquired over a wide azimuth range using long offsets. For such data, optimum imaging and subsequent quantitative amplitude interpretation requires taking subsurface anisotropy adequately into account during execution of the quantitative interpretation workflow. Here, we present a multi‐objective approach to find an optimal solution using both well logs and seismic data. We include minimization of a seismic match objective function as a constraint to narrow the uncertainty distribution around model parameters and to ensure that the model is consistent with seismic as well as well log data. Consequently, the resulting anisotropy model can be used for both well logs and seismic data analysis. First, the Hudson‐Cheng crack model is used to obtain rock matrices properties and aspect ratio of a set of ellipsoidal cracks. Then, we obtain a set of non‐dominated solutions, which minimizes the rock physics model multi‐parameter objective function and the Amplitude‐Versus‐Offset objective function. The approach is applied to field data with one vertical well log and pre‐stack migrated seismic data. In spite of the low signal‐to‐noise ratio of the seismic data, the overall results are consistent with the rock physics model and fit the seismic amplitude variations, particularly for the confidently interpretable mid‐to‐far angles of incidence. Furthermore, we extend the approach to predict seismic anisotropy away from well calibration, to map the occurrence of high‐quality organic‐rich shales.
Hidden Stores of Organic Matter in Northern Lake Ice: Selective Retention of Terrestrial Particles, Phytoplankton and Labile Carbon
Authors: Imbeau Elise , Vincent Warwick F. , Wauthy Maxime , Cusson Mathieu , Rautio Milla 
Published: July 2021

AbstractAround 50% of the world's lakes freeze seasonally, but the duration of ice‐cover is shortening each year and this is likely to have broad limnological consequences. We sampled freshwater ice and the underlying water in 19 boreal and polar lakes to evaluate whether lake ice contains an inoculum of algae, nutrients, and carbon that may contribute to lake ecosystem productivity. Boreal and Arctic lakes differed in ice duration (6 vs. >10 months), thickness (70 vs. 190 cm), and quality (predominantly snow ice vs. black ice), but in all lakes, there were consistent differences in biological and biogeochemical composition between ice and water. Particulate fractions were often more retained while most dissolved compounds were excluded from the ice; for example, the ice had more terrestrial particulate carbon, measured as fatty acid biomarkers (averages of 1.1 vs. 0.3 µg L−1) but lower dissolved organic carbon (2.2 vs. 5.7 mg C L−1) and inorganic phosphorus concentrations (4.0 vs. 7.5 µg C L−1) than the underlying water. The boreal ice further had three times higher chlorophyll‐a, than the water (0.9 vs. 0.3 µg L−1). Of the dissolved fractions, the contribution of protein‐like compounds was higher in the ice, and this in all lakes. These labile compounds would become available to planktonic microbes when the ice melts. Our results show that freshwater ice has an underestimated role in storage and transformation in the biogeochemical carbon cycle of ice‐covered lake ecosystems.
A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers
Authors: Hamalian Sarkis , Güth Robert , Runa Farhana , Sanchez Francesca , Vickers Eric , Agajanian Megan , Molnar Justin , Nguyen Tuan , Gamez Joshua , Humphries Jonathan D. , Nayak Anupma , Humphries Martin J. , Tchou Julia , Zervantonakis Ioannis K. , Kelber Jonathan A. 
Published: July 2021

AbstractIntercellular mechanisms by which the stromal microenvironment contributes to solid tumor progression and targeted therapy resistance remain poorly understood, presenting significant clinical hurdles. PEAK1 (Pseudopodium-Enriched Atypical Kinase One) is an actin cytoskeleton- and focal adhesion-associated pseudokinase that promotes cell state plasticity and cancer metastasis by mediating growth factor-integrin signaling crosstalk. Here, we determined that stromal PEAK1 expression predicts poor outcomes in HER2-positive breast cancers high in SNAI2 expression and enriched for MSC content. Specifically, we identified that the fibroblastic stroma in HER2-positive breast cancer patient tissue stains positive for both nuclear SNAI2 and cytoplasmic PEAK1. Furthermore, mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) express high PEAK1 protein levels and potentiate tumorigenesis, lapatinib resistance and metastasis of HER2-positive breast cancer cells in a PEAK1-dependent manner. Analysis of PEAK1-dependent secreted factors from MSCs revealed INHBA/activin-A as a necessary factor in the conditioned media of PEAK1-expressing MSCs that promotes lapatinib resistance. Single-cell CycIF analysis of MSC-breast cancer cell co-cultures identified enrichment of p-Akthigh/p-gH2AXlow, MCL1high/p-gH2AXlow and GRP78high/VIMhigh breast cancer cell subpopulations by the presence of PEAK1-expressing MSCs and lapatinib treatment. Bioinformatic analyses on a PEAK1-centric stroma-tumor cell gene set and follow-up immunostaining of co-cultures predict targeting antiapoptotic and stress pathways as a means to improve targeted therapy responses and patient outcomes in HER2-positive breast cancer and other stroma-rich malignancies. These data provide the first evidence that PEAK1 promotes tumorigenic phenotypes through a previously unrecognized SNAI2-PEAK1-INHBA stromal cell axis.