bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL
Authors: Jayappa Kallesh D. , Gordon Vicki L. , Morris Christopher G. , Wilson Briana , Shetty B. Dharmaveer , Cios Konrad J. , Arora Puja C. , Isaac Krista M. , Saha Shekhar , Bender Timothy P. , Williams Michael E. , Portell Craig A. , Weber Michael J. 
Published: August 2021

AbstractThe Bcl-2 inhibitor venetoclax has yielded exceptional clinical responses in chronic lymphocytic leukemia (CLL). However, de novo resistance can result in failure to achieve negative minimal residual disease and predicts poor treatment outcomes. Consequently, additional proapoptotic drugs, such as inhibitors of Mcl-1 and Bcl-xL, are in development. By profiling antiapoptotic proteins using flow cytometry, we find that leukemic B cells that recently emigrated from the lymph node (CD69+/CXCR4Low) in vivo are enriched for cell clusters simultaneously overexpressing multiple antiapoptotic proteins (Mcl-1High/Bcl-xLHigh/Bcl-2High) in both treated and treatment-naive CLL patients. These cells exhibited antiapoptotic resistance to multiple BH-domain antagonists, including inhibitors of Bcl-2, Mcl-1, and Bcl-xL, when tested as single agents in a flow cytometry–based functional assay. Antiapoptotic multidrug resistance declines ex vivo, consistent with resistance being generated in vivo by extrinsic microenvironmental interactions. Surviving “persister” cells in patients undergoing venetoclax treatment are enriched for CLL cells displaying the functional and molecular properties of microenvironmentally induced multidrug resistance. Overcoming this resistance required simultaneous inhibition of multiple antiapoptotic proteins, with potential for unwanted toxicities. Using a drug screen performed using patient peripheral blood mononuclear cells cultured in an ex vivo microenvironment model, we identify novel venetoclax drug combinations that induce selective cytotoxicity in multidrug-resistant CLL cells. Thus, we demonstrate that antiapoptotic multidrug-resistant CLL cells exist in patients de novo and show that these cells persist during proapoptotic treatment, such as venetoclax. We validate clinically actionable approaches to selectively deplete this reservoir in patients.
Implication of Retrobulbar and internal carotid artery blood-flow-volume alterations for the pathogenesis of non-arteritic anterior ischemic optic neuropathy
Authors: Fu Zhiyong , Li Hongyang , Wang Yanling 
Published: August 2021

Abstract
Background
To analyze blood flow volume alteration that involved both retrobulbar artery and internal carotid artery (ICA) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) and to assess their relevance for the pathogenesis of NAION.

Methods
Forty two patients with NAION (unilateral affected) and 42 age-matched controls participated in this study. By head-and-neck computed tomographic angiography (CTA), the diameter of ICA and ophthalmic artery (OA) were measured. By colour Doppler imaging (CDI), the mean blood flow velocity (Vm) and the blood flow volume of ICA and OA were measured or calculated. By optical coherence tomography angiography (OCTA), peripapillary and optic disc vessel density were measured. Data obtained from the affected side of the patients were compared to those of the contralateral healthy side and the control.

Results
Compared with the controls and the contralateral healthy side of the patients with NAION, the diameter of ICA, the blood flow volume of ICA and OA, the peripapillary and optic disc vessel density in the affected side decreased significantly (p < 0.05). However, there was no statistical difference in the diameter of OA (p = 0.179, 0.054 respectively), the Vm of OA (p = 0.052, 0.083 respectively), or the Vm of ICA (p = 0.364, 0.938 respectively) between groups. Peripapillary and optic disc vessel density were significantly positive correlated with the blood flow volume in ipsilateral ICA and OA in patients with NAION (all p < 0.01).

Conclusions
The reduction of blood flow volume was more prominent in OA and ICA than decrease of Vm, peripapillary and optic disc vessel density were significantly positive correlated with the blood flow volume of ipsilateral ICA and OA in patients with NAION.
Promoting helpful attention and interpretation patterns to reduce anxiety and depression in young people: weaving scientific data with young peoples’ lived experiences
Authors: Lau Jennifer Y. F. , Watkins-Muleba Rebecca , Lee Isabelle , Pile Victoria , Hirsch Colette R. 
Published: August 2021

AbstractBackgroundAnxiety and depression are common, disabling and frequently start in youth, underscoring the need for effective, accessible early interventions. Empirical data and consultations with lived experience youth representatives suggest that maladaptive cognitive patterns contribute to and maintain anxiety and depression in daily life. Promotingadaptivecognitive patterns could therefore reflect “active ingredients” in the treatment and/or prevention of youth anxiety and depression. Here, we described and compared different therapeutic techniques that equipped young people with a more flexible capacity to use attention and/or promoted a tendency to positive/benign (over threatening/negative) interpretations of uncertain situations.MethodsWe searched electronic databases (PubMed, PsycINFO, EMBASE, and PsycARTICLES) for studies containing words relating to: intervention; youth; anxiety and/or depression and attention and/or interpretation, and selected studies which sought to reduce self-reported anxiety/depression in youth by explicitly altering attention and/or interpretation patterns. Ten young people with lived experiences of anxiety and depression and from diverse backgrounds were consulted on the relevance of these strategies in managing emotions in their daily lives and also whether there were additional strategies that could be targeted to promote adaptive thinking styles.ResultsTwo sets of techniques, each targeting different levels of responding with different strengths and weaknesses were identified. Cognitive bias modification training (CBM) tasks were largely able to alter attention and interpretation biases but the effects of training on clinical symptoms was more mixed. In contrast, guided instructions that teach young people to regulate their attention or to evaluate alternative explanations of personally-salient events, reduced symptoms but there was little experimental data establishing the intervention mechanism. Lived experience representatives suggested that strategies such as deliberately recalling positive past experiences or positive aspects of oneself to counteract negative thinking.DiscussionCBM techniques target clear hypothesised mechanisms but require further co-design with young people to make them more engaging and augment their clinical effects. Guided instructions benefit from being embedded in clinical interventions, but lack empirical data to support their intervention mechanism, underscoring the need for more experimental work. Feedback from young people suggest that combining complimentary techniques within multi-pronged “toolboxes” to develop resilient thinking patterns in youth is empowering.
Practice variation in the informed consent procedure for thrombolysis in acute ischemic stroke: a survey among neurologists and neurology residents
Authors: Zonjee Valentijn J. , Slenders Jos P. L. , de Beer Frank , Visser Marieke C. , ter Meulen Bastiaan C. , Van den Berg-Vos Renske M. , van Schaik Sander M. 
Published: August 2021

AbstractBackgroundObtaining informed consent for intravenous thrombolysis in acute ischemic stroke can be challenging, and little is known about if and how the informed consent procedure is performed by neurologists in clinical practice. This study examines the procedure of informed consent for intravenous thrombolysis in acute ischemic stroke in high-volume stroke centers in the Netherlands.MethodsIn four high volume stroke centers, neurology residents and attending neurologists received an online questionnaire concerning informed consent for thrombolysis with tissue-type plasminogen activator (tPA). The respondents were asked to report their usual informed consent practice for tPA treatment and their considerations on whether informed consent should be obtained.ResultsFrom the 203 invited clinicians, 50% (n = 101) completed the questionnaire. One-third of the neurology residents (n = 21) and 21% of the neurologists (n = 8) reported that they always obtain informed consent for tPA treatment. If a patient is not capable of providing informed consent, 30% of the residents (n = 19) reported that they start tPA treatment without informed consent. In these circumstances, 53% of the neurologists (n = 20) reported that the resident under their supervision would start tPA treatment without informed consent. Most neurologists (n = 21; 55%) and neurology residents (n = 45; 72%) obtained informed consent within one minute. None of the respondents used more than five minutes for informed consent. Important themes regarding obtaining informed consent for treatment were patients’ capacity, and medical, ethical and legal considerations.ConclusionThe current practice of informed consent for thrombolysis in acute ischemic stroke varies among neurologists and neurology residents. If informed consent is obtained, most clinicians stated to obtain informed consent within one minute. In the future, a shortened information provision process may be applied, making a shift from informed consent to informed refusal, while still considering the patient’s capacity, stroke severity, and possible treatment delays.
Linear analysis on the onset of thermal convection of highly compressible fluids with variable viscosity and thermal conductivity in spherical geometry: implications for the mantle convection of super-Earths
Authors: Kameyama Masanori 
Published: August 2021

AbstractIn this paper, we carried out a series of linear analyses on the onset of thermal convection of highly compressible fluids whose physical properties strongly vary in space in convecting vessels either of a three-dimensional spherical shell or a two-dimensional spherical annulus geometry. The variations in thermodynamic properties (thermal expansivity and reference density) with depth are taken to be relevant for the super-Earths with ten times the Earth’s mass, while the thermal conductivity and viscosity are assumed to exponentially depend on depth and temperature, respectively. Our analysis showed that, for the cases with strong temperature dependence in viscosity and strong depth dependence in thermal conductivity, the critical Rayleigh number is on the order of 108–109, implying that the mantle convection of massive super-Earths is most likely to fall in the stagnant-lid regime very close to the critical condition, if the properties of their mantle materials are quite similar to the Earth’s. Our analysis also demonstrated that the structures of incipient flows of stagnant-lid convection in the presence of strong adiabatic compression are significantly affected by the depth dependence in thermal conductivity and the geometries of convecting vessels, through the changes in the static stability of thermal stratification of the reference state. When the increase in thermal conductivity with depth is sufficiently large, the thermal stratification can be greatly stabilized at depth, further inducing regions of insignificant fluid motions above the bottom hot boundaries in addition to the stagnant lids along the top cold surfaces. We can therefore speculate that the stagnant-lid convection in the mantles of massive super-Earths is accompanied by another motionless regions at the base of the mantles if the thermal conductivity strongly increases with depth (or pressure), even though their occurrence is hindered by the effects the spherical geometries of convecting vessels.
The difficulty of continuing sports activities after open-wedge high tibial osteotomy in patient with medial knee osteoarthritis: a retrospective case series at 2-year-minimum follow-up
Authors: Maeda Shugo , Chiba Daisuke , Sasaki Eiji , Oyama Tetsushi , Sasaki Tomoyuki , Otsuka Hironori , Ishibashi Yasuyuki 
Published: August 2021

AbstractPurposeThis study aimed to investigate the rate at which patients returned to sports after open wedge high tibial osteotomy and identify the continuity of sports activity post-operatively.MethodsThirty-five patients (40 knees) who underwent open-wedge high tibial osteotomy (OW-HTO) in medial knee osteoarthritis were included in this study. The mean age of the patients who underwent surgery was 55.1 ± 10.7 years, and the mean follow-up period was 41.0 ± 24.7 months. Clinical results and radiographic parameters calculated in standing whole-leg radiographs preoperatively, post-operatively, and at the final follow-up were evaluated.ResultsThirty-one patients (88.6%) were able to return to preoperative sports activity; however, only 14 patients (40.0%) completely returned to preoperative sports activity levels. Of the 31 patients who returned to sports activity, 10 patients (32.3%) maintained post-operative sporting activity levels at the final follow-up. In radiographic parameters, the weight-bearing line ratio was considered loss of correction in the post-operative period leading to the final follow-up. Patients who completely returned to sports and maintained sporting activity levels at the final follow-up had significantly higher the Knee Injury and Osteoarthritis Outcome Score pain subscale values and lower visual analogue scale of knee pain at pre-surgery and final follow-up than other patients, including those who partially returned to sports.ConclusionsThe proportion of patients who returned to sports after OW-HTO and were able to participate in competitions at the same activity level as before surgery was low and insufficient.Level of evidenceRetrospective case series, IV
Profiling Combat Sports Athletes: Competitive History and Outcomes According to Sports Type and Current Level of Competition
Authors: Barley Oliver R. , Harms Craig A. 
Published: August 2021

Abstract
Background
This study aimed to investigate the competitive history (the age when training and competing started), training habits and patterns of winning and losing of competitive combat sports athletes across different combat sports as well as the level of competition (e.g. amateurs, state-level and elite).

Methods
Competitors (N = 298) from mixed martial arts (MMA), Muay Thai/kickboxing, boxing, Brazilian jiu-jitsu (BJJ), wrestling, judo and traditional striking sports (TSS) completed an online questionnaire.

Results
Most athletes began competing in their mid-teenage years and competing soon after except for wrestlers who began earlier. Elite athletes began training earlier than amateurs (13.75 ± 7.75 years and 16.2 ± 7.45 years, p<0.01, respectively). Training habits were similar across sports (~4 combat and ~3 non-combat training sessions per week), except for MMA and wrestling which did more combat sports-specific training than Judo and TSS. Wrestlers did more non-combat sports-specific training than all other sports. Elite athletes completed more combat sessions per week than their lower-level contemporaries (4.64 ± 2.49 and 3.9 ± 1.44, p=0.01, respectively). Patterns of winning or losing were consistent across sports, except for amateur athletes who were more likely to report all their victories by points and none of their victories by submission or pin. Additionally, elite athletes are less likely to report none of their victories coming by knockout.

Conclusions
Results may indicate that finishing ability is a key distinguisher of competitive level. The present study provides normative data for training and competing habits for athletes, support staff and regulators to use.
Large California wildfires: 2020 fires in historical context
Authors: Keeley Jon E. , Syphard Alexandra D. 
Published: August 2021

AbstractBackgroundCalifornia in the year 2020 experienced a record breaking number of large fires. Here, we place this and other recent years in a historical context by examining records of large fire events in the state back to 1860. Since drought is commonly associated with large fire events, we investigated the relationship of large fire events to droughts over this 160 years period.ResultsThis study shows that extreme fire events such as seen in 2020 are not unknown historically, and what stands out as distinctly new is the increased number of large fires (defined here as > 10,000 ha) in the last couple years, most prominently in 2020. Nevertheless, there have been other periods with even greater numbers of large fires, e.g., 1929 had the second greatest number of large fires. In fact, the 1920’s decade stands out as one with many large fires.ConclusionsIn the last decade, there have been several years with exceptionally large fires. Earlier records show fires of similar size in the nineteenth and early twentieth century. Lengthy droughts, as measured by the Palmer Drought Severity Index (PDSI), were associated with the peaks in large fires in both the 1920s and the early twenty-first century.
The effect of using technology for work on burnout and work productivity among Saudi board residents: a cross-sectional study
Authors: Al-Khudhayr Abrar Mohammad , Al-Shaghab Mariyyah Ahmad , Al-Jabr Qasem Mohammad 
Published: August 2021

Abstract
Background
The use of technology for work has become an unavoidable component of most occupations. It is considered a double-edged sword; it has a massive impact on employees’ mental health and productivity, mainly when used outside the working hours. This practice is referred to as technology-assisted supplemental work (TASW). This study aimed to determine the effect of supplemental work using technology behavior on burnout levels among Saudi board residents and its consequences on work productivity.

Results
Three hundred seventy-seven residents were involved in this study to assess their TASW behavior, burnout level, and presenteeism. The Maslach Burnout Inventory (MBI) scale is used to assess burnout, which is composed of three subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). This study revealed that a high risk of EE was found among 52.5% of residents, 12.2% were at high risk of DP, and 53.1% had low PA. The mean score of TASW was 19.7 (SD 3.75) out of 30 points, while the mean score of presenteeism (SPS-6) was 18.5 (SD 4.49) out of 30 points. A significant correlation was found between SPS-6 and MBI subscales including emotional exhaustion (r=−0.642, p<0.001), depersonalization (r=−0.406, p<0.001), and personal accomplishment (r=0.206, p<0.001), but association with TASW did not reach statistical significance (p>0.05).

Conclusion
Burnout “specifically Emotional Exhaustion” was noted to be significantly high among residents in different specialties in Saudi Arabia. Furthermore, several factors in the study were evidently demonstrated to be highly related to burnout which is directly associated with lost work productivity. However, our study suggests that extra working hours at home using technology were not associated with burnout or an increase in productivity.
Clinical correlates of circulating cell-free DNA tumor fraction
Authors: Bredno Joerg , Lipson Jafi , Venn Oliver , Aravanis Alexander M. , Jamshidi Arash 
Published: August 2021

BackgroundOncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated.Methods and findingsCirculating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test.ConclusionsPrognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.
Endoscopy-Induced Pancreatic Pseudocyst Rupture: A Case of Secondary Peritonitis After Upper Endoscopy
Authors: Robbins Gordon , Kantsevoy Sergey , Raina Amit 
Published: August 2021

ABSTRACT
Pancreatic pseudocysts are often drained endoscopically after 4–6 weeks of maturation. Allowing for developed encapsulation ensures that the cyst walls are strong enough to sustain drainage. However, in 3%–5% of these cases, pseudocysts will rupture spontaneously and put patients at risk of peritonitis. We present the first documented case of pancreatic pseudocyst rupture after upper endoscopy. Exploratory laparotomy confirmed the absence of viscus perforation and highlighted the danger of any procedure that increases intra-abdominal pressure in a patient with a pancreatic pseudocyst. Awareness of this complication should impact our decision when considering endoscopy in patients with pancreatic pseudocysts.
Gender Differences in the Returns to Education over Time for Married Couples
Authors: Brendemuehl Nikki , Jolly Nicholas A. 
Published: August 2021

Abstract
Using US Census data from 1960 to 2000 and American Community Survey data from 2010, this paper analyzes gender differences in the return to education for married couples. Results from this analysis show that the return to schooling has increased over time for both genders; however, the relative return to schooling for females has fallen since the 1990s. In 2010, married women who are under age 35 and are in the top 20 percent of the income distribution had lower returns to schooling compared to men. These results are consistent with several demographic shifts that occurred during the last half of the 20th century.
If U.S. Citizens Pose a Risk to International Health, Can the Federal Government Prevent Them from Traveling Abroad?
Authors: Clark Melissa 
Published: August 2021

Abstract
While states normally controlling public health emergencies, this article discusses the current Centers for Disease Control and Prevention regulations to determine whether the federal agency has the authority to stop ill U.S. citizens from traveling abroad in the event of a public health emergency. The article compares state, federal, and international laws. It also provides an in-depth history of federal quarantine and health recommendations and compares that prior history with the current COVID-19 pandemic.