bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective treatment in lung adenocarcinoma patient with brain metastases harboring novel CLHC1/RNT4 intergenic region- ALK fusion
Authors: Xia Huanling , Liang Binbin , Liu Guoxiang , Qi Yingxue , Luo Ningning , Li Mengmeng 
Published: April 2022

Abstract

Rationale:
Anaplastic lymphoma kinase (ALK) fusion, an important oncogenic mutation, occurs in 3% to 7% of non-small cell lung cancer (NSCLC) cases, and EML4 is the most common partner gene. With the widespread application of next-generation sequencing (NGS), more gene breakpoint fusions have been discovered and functional fusion transcripts can provide targeted clinical benefits.

Patient concerns and diagnosis:
A 40-year-old woman was diagnosed with lung adenocarcinoma with brain metastases. A novel CLHC1/RNT4 intergenic region, ALK (Exon20-29) (abundance 39.97%), was identified using lung puncture tissue by NGS analysis (Simceredx), and results of immunohistochemistry and fluorescence in situ hybridization confirmed ALK fusion.

Interventions and outcomes:
The patient was administered oral crizotinib (250 mg bid) combined with endostar (30 mg d1-7) for 12 cycles from June 18, 2020. The patient's condition was controlled, and the curative effect was evaluated as stable disease (SD). Unfortunately, brain magnetic resonance images showed multiple nodules in the left cerebellar hemisphere, and chest computed tomography showed no significant changes in the progression of the disease. Subsequently, alectinib (600 mg bid) was administered on April 1, 2021. Brain lesions were significantly reduced and partial remission (PR) was achieved. No significant changes were observed in the lung lesions.

Lessons:
ALK fusion is a risk factor for brain metastasis (BM) in patients with advanced non-small NSCLC patients. In our case, a novel CLHC1/RNT4 intergenic region, ALK fusion, was identified for the first time in a lung adenocarcinoma patient with BM, who benefited from crizotinib and endostar sequential alectinib. Our case highlights the advantages of NGS for fusion detection and provides promising treatment options for NSCLC patients with BM harboring ALK fusions.
Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases
Authors: Shieh Li-Tsun , Lee Sung-Wei , Chen Chia-Chun , Ho Yi-Chia , Wang Yu-Wen , Ho Sheng-Yow 
Published: April 2022

Abstract
Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.
We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.
Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.
We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.
“The More We Know, the More We're Able to Help”: Participatory Development of an Evaluation Framework for Community Health Worker Programs
Authors: Sherman Mya , Covert Hannah H. , Lichtveld Maureen Y. 
Published: April 2022

Context:
It is critical to evaluate community health worker (CHW) programs to maximize effectiveness. However, there is little consensus, and structure, for how to evaluate such programs.

Objective:
The purpose of this study was to develop a flexible framework for evaluating components of CHW programs in community and clinical settings.

Design:
Semistructured interviews were conducted with CHWs and their supervisors to determine evaluation categories for the framework. A survey was then administered to pilot the framework at federally qualified health centers and community-based organizations with existing CHW programs.

Setting:
Eighteen federally qualified health centers and community-based organizations in Louisiana, Mississippi, Alabama, and Florida.

Participants:
Participants consisted of 23 CHWs and 19 CHW supervisors.

Results:
Interview participants directly informed the development of an evaluation framework for CHW programs. The framework consists of 7 evaluation categories: client relations, intraorganizational relations, interorganizational relations, capacity development, program effectiveness, cost-efficiency, and sustainability. Survey respondents specified best practices for program implementation for each evaluation category. Recommendations for CHW program evaluation include tailoring evaluation efforts and data collection methods to program context, using mixed-methods approaches for collecting evaluation data, and streamlining evaluation efforts with an organization's existing evaluation systems.

Conclusions:
The evaluation framework is a flexible and practical model for collecting information needed for monitoring and evaluating CHW programs. By relying on practitioners' perspectives, this study contributes to an evidence base for implementing and evaluating CHW programs.
Developing a National Trauma Research Action Plan: Results from the acute resuscitation, initial patient evaluation, imaging, and management research gap Delphi survey
Authors: Costantini Todd W. , Galante Joseph M. , Braverman Maxwell A. , Phuong Jim , Price Michelle A. , Cuschieri Joseph , Godat Laura N. , Holcomb John B. , Coimbra Raul , Bulger Eileen M. ,   NTRAP Acute Resuscitation Panel
Published: April 2022

BACKGROUND
Injury is the leading cause of death in patients aged 1 to 45 years and contributes to a significant public health burden for individuals of all ages. To achieve zero preventable deaths and disability after injury, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan to improve outcomes for military and civilian trauma patients. Because rapid resuscitation and prompt identification and treatment of injuries are critical in achieving optimal outcomes, a panel of experts was convened to generate high-priority research questions in the areas of acute resuscitation, initial evaluation, imaging, and definitive management on injury.

METHODS
Forty-three subject matter experts in trauma care and injury research were recruited to perform a gap analysis of current literature and prioritize unanswered research questions using a consensus-driven Delphi survey approach. Four Delphi rounds were conducted to generate research questions and prioritize them using a 9-point Likert scale. Research questions were stratified as low, medium, or high priority, with consensus defined as ≥60% of panelists agreeing on the priority category. Research questions were coded using a taxonomy of 118 research concepts that were standard across all National Trauma Research Action Plan panels.

RESULTS
There were 1,422 questions generated, of which 992 (69.8%) reached consensus. Of the questions reaching consensus, 327 (33.0%) were given high priority, 621 (62.6%) medium priority, and 44 (4.4%) low priority. Pharmaceutical intervention and fluid/blood product resuscitation were most frequently scored as high-priority intervention concepts. Research questions related to traumatic brain injury, vascular injury, pelvic fracture, and venous thromboembolism prophylaxis were highly prioritized.

CONCLUSION
This research gap analysis identified more than 300 high-priority research questions within the broad category of Acute Resuscitation, Initial Evaluation, Imaging, and Definitive Management. Research funding should be prioritized to address these high-priority topics in the future.
A comparison of management and outcomes following blunt versus penetrating pancreatic trauma: A secondary analysis from the Western Trauma Association Multicenter Trials Group on Pancreatic Injuries
Authors: Biffl Walter L. , Ball Chad G. , Moore Ernest E. , West Michaela , Russo Rachel M. , Balogh Zsolt , Kornblith Lucy , Callcut Rachael , Schaffer Kathryn B. , Castelo Matthew ,   the WTA Multicenter Trials Group on Pancreatic Injuries
Published: April 2022

BACKGROUND
The impact of injury mechanism on outcomes of pancreatic trauma has not been well studied, and current guidelines do not differentiate recommendations for blunt and penetrating injuries. The purpose of this study was to analyze interventions and outcomes as they relate to mechanism. We hypothesized that penetrating pancreatic trauma results in greater morbidity than blunt trauma because of more frequent operative exploration without imaging and thus more aggressive surgical management.

METHODS
Secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018 was performed. Deaths within 24 hours of admission were excluded from analysis of the primary outcome, pancreas-related complications (PRCs). Data were analyzed by injury mechanism using various statistical tests where appropriate.

RESULTS
Thirty-three centers reported on 1,240 patients (44% penetrating). Penetrating trauma patients were twice as likely to undergo resection (45% vs. 23%) and suffer PRCs (39% vs. 20%). However, differences varied widely based on injury grade and management. There were fewer resections and more nonoperative management in blunt grades I to III injury. Pancreas-related complications occurred in 40% of high-grade injuries with no difference between mechanisms and in 40% of patients after resection, regardless of mechanism or injury grade. High-grade pancreatic injury (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.55–3.67), penetrating injury (OR, 1.99; 95% CI, 1.31–3.05), and management in a low-volume center (i.e., five or fewer cases/year) (OR, 1.65; 95% CI, 1.16–2.35) were independent predictors of PRCs.

CONCLUSION
Management of grades I to III, but not grades IV/V, pancreatic injuries varies based on mechanism. Penetrating injury is an independent risk factor for PRCs, but main pancreatic duct injury and resection are associated with high rates of PRCs regardless of the injury mechanism. Resection appears to offer better outcomes for grade IV/V injuries, and grade I and II injuries should be managed nonoperatively.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Hemodynamic events during en route critical care for patients with traumatic brain injury
Authors: Davis William T. , Medellin Kimberly L. , Cutright Julie E. , Arana Allyson A. , Strilka Richard , Sorensen Derek , Maddry Joseph K. , Savell Shelia C. , Ng Patrick C. 
Published: April 2022

BACKGROUND
Exposure to stressors of flight may increase risk of secondary insults among critically injured combat casualties wounded with traumatic brain injury (TBI). The primary objective of this study was to describe the prevalence of hemodynamic events by phase of transport among patients with TBI transported by Critical Care Air Transport Teams (CCATT).

METHODS
We performed a secondary analysis of a retrospective cohort of 477 adults with moderate to severe TBI, who required transport by CCATT to Germany from multiple hospitals in the Middle East between January 2007 and May 2014. We abstracted clinical data from handwritten CCATT medical records. Hemodynamic events included systolic blood pressure <100 mm Hg and cerebral perfusion pressure <60 mm Hg. We calculated the proportion of patients experiencing hemodynamic events for each phase of flight.

RESULTS
We analyzed 404 subjects after exclusions for catastrophic brain injury (n = 39) and missing timestamps (n = 34). Subjects had high Injury Severity Scores (median, 29; interquartile range [IQR], 21–35) and a median flight time of 423 minutes (IQR, 392.5–442.5 minutes). The median of documented in-flight vital signs was 8 measurements (IQR, 6.5–8 measurements). Documented systolic blood pressure in-flight events occurred in 3% of subjects during ascent, 7.9% during early flight, 7.7% during late flight, and 2.2% during descent, with an overall in-flight prevalence of 13.9%. Among patients with intracranial pressure monitoring (n = 120), documented cerebral perfusion pressure events occurred in 5% of subjects during ascent, 23% during early flight, 17% during late flight, and 5.8% during descent, with an overall in-flight prevalence of 30.8%.

CONCLUSION
Documented hemodynamic events occurred during each phase of flight in severely injured combat casualties wounded with TBI, and episodic documentation likely underestimated the actual in-flight frequency of secondary insults.

LEVEL OF EVIDENCE
Prognostic and epidemiological; Level IV.
Postinjury platelet aggregation and venous thromboembolism
Authors: Matthay Zachary A. , Hellmann Zane J. , Nunez-Garcia Brenda , Fields Alexander T. , Cuschieri Joseph , Neal Matthew D. , Berger Jeffrey S. , Luttrell-Williams Elliot , Knudson M. Margaret , Cohen Mitchell J. , Callcut Rachael A. , Kornblith Lucy Z. 
Published: April 2022

BACKGROUND
Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE.

METHODS
We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011–2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE.

RESULTS
The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 109/L vs. 164 × 109/L, p = 0.01) and lower PA in response to ADP (p < 0.05), collagen (p < 0.05), and thrombin (p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [p = 0.03]; δ-collagen, 1.36 [p = 0.01]; δ-thrombin, 1.41 [p < 0.01]).

CONCLUSION
Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens.

LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level III.
Estimating the risk of hospitalisation and death in England’s remaining unvaccinated population
Authors: Shingleton Joseph , Dyke Steven , Herrick Archie , Walker Brodie , Finnie Thomas 
Published: April 2022

AbstractThe roll-out of COVID-19 vaccines in the England has generally been very good – with over 80% of over 12s having received two doses of vaccine by the start of February 2022, and 67% having received a further booster dose. Despite this, there is a small section of the population who remain unvaccinated, either due to lack of access, hesitancy or resistant to vaccination. In this report we estimate that, during 2021, there were approximately 3,500 deaths in unvaccinated people, who could otherwise have reasonably been expected to receive a vaccination. Further, we show that if all of the remaining unvaccinated population in England were to become infected (or reinfected) with the Omicron variant of COVID-19, we would expect to see approximately 11,700 further deaths and 29,600 hospitalisations. These number could fall to 5,300 and 19,600 respectively, if all but the most vaccine resistant individuals become fully vaccinated.
Persistent cross-species SARS-CoV-2 variant infectivity predicted via comparative molecular dynamics simulation
Authors: Rajendran Madhusudan , Babbitt Gregory A. 
Published: April 2022

AbstractWidespread human transmission of SARS-CoV-2 highlights the substantial public health, economic, and societal consequences of virus spillover from wildlife and also presents a repeated risk of reverse spillovers back to naïve wildlife populations. We employ comparative statistical analyses of a large set of short-term molecular dynamic (MD) simulations to investigate potential human to bat (Rhinolophus macrotis) cross-species infectivity allowed by the binding of SARS-CoV-2 receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) across the bat progenitor strain and emerging human strain variants of concern (VOC). We statistically compare the dampening of atom motion during binding across protein sites upon the formation of the RBD/ACE2 binding interface using bat vs. human target receptors (i.e. bACE2 and hACE2). We report that while the bat progenitor viral strain RaTG13 shows some pre-adaption to binding hACE2, it also exhibits stronger overall affinity to bACE2. However, while the early emergent human strains and later VOC’s exhibit robust binding to both hACE2 and bACE2, the delta and omicron variants exhibit evolutionary adaption of binding to hACE2. However, we conclude there is a still significant risk of mammalian cross-species infectivity of human VOC’s during upcoming waves of infection as COVID-19 transitions from a pandemic to endemic status.
The role of environmental calcium in the extreme acid tolerance of northern banjo frog (Limnodynastes terraereginae) larvae
Authors: Hird Coen , Franklin Craig E. , Cramp Rebecca L. 
Published: April 2022

ABSTRACTMany aquatically respiring animals inhabiting low pH waters can suffer acute inhibition of ion uptake and loss of branchial (gill) epithelial integrity, culminating in a fatal, rapid loss of body Na+. Environmental calcium levels ([Ca2+]e) are pivotal in maintaining branchial junction integrity, with supplemental Ca2+reversing the negative effects of low pH in some animals. Tolerance of some naturally acidic environments by aquatic animals is further complicated by low [Ca2+]e, yet many of these environments are surprisingly biodiverse. How these animals overcome the combined damaging actions of low pH and low environmental Ca2+remains unknown. Here, we examined the effects of [Ca2+]eon the response to low pH in larvae of the highly acid tolerant frogLimnodynastes terraereginae. Acute exposure to low pH water in the presence of low [Ca2+]eincreased net Na+efflux. Provision of additional [Ca2+]ereduced net Na+efflux, but the effect was saturable. Acclimation to both low and high [Ca2+]eimproved the resistance of larvae to Na+efflux at low pH. Inhibition of apical Ca2+uptake by ruthenium red resulted in an abrupt loss of tolerance to low pH in larvae acclimated to low pH water. Acclimation to acidic water increased branchial gene expression of the intracellular Ca2+transport protein calbindin, consistent with a role for increased transcellular Ca2+trafficking in the tolerance of acidic water. This study confirmed the physiological challenge of low [Ca2+]eon branchial integrity in acidic waters and highlighted a potential role for maintenance of transcellular Ca2+uptake in the acid tolerance ofL. terraereginae.Summary statementTolerance of naturally acidic, dilute, and soft waters by larvae of the frogLimnodynastes terraereginaeinvolves adaptations to the branchial calcium transport pathway which protects intercellular junctions against damage.
A Chitin-Binding Protein Ultra-highly expressed in the Outer Fold of Mantle is Related to Shell Colour in Pacific Oyster Crassostrea gigas
Authors: Li Mai , Tang Juyan , Huang Baoyu , Liu Yaqiong , Wei Lei , Han Yijing , Wang Xiaona , Sang Xiuxiu , Yuan Mengqiang , Fan Nini , Cai Shuai , Zheng Yanxin , Zhang Meiwei , Wang Xiaotong 
Published: April 2022

AbstractMolluscs constitute the second largest phylum of animals in the world, and shell colour and stripes are one of their most important phenotypic characteristics. Studies on the mechanism of shell pigmentation help understand the evolutionary and ecological significance of shell colour and serve as the basis for shell colour breeding. In this study, a matched-pair design was used in comparing the black- and white-striped mantles of the same oyster. The result showed that the stripes of shell surface are corresponding to the stripes of the mantle edge. Transcriptomic analysis identified an uncharacterized protein gene (we named it as Crassostrea gigas chitin-binding protein, CgCBP) highly expressed in the black mantles. Three folds (inner fold, middle fold and outer fold) were found on the mantle edge of oyster, but only the outer fold has the same colour as the shell. Transcriptomic comparison indicated that the three folds of the mantle edge are functionally differentiated, and the CgCBP gene is ultra-highly expressed only in the outer fold. We obtained new black and white shell periostraca from the shell notching experiment and found their structural differences by scanning electron microscope. Chitin was successfully extracted and identified from the shell periostraca. Proteomic analysis revealed differences in protein composition between the two shell periostraca. Particularly, the black shell periostraca have more proteins related to melanin biosynthesis and chitin binding compared with the white ones, and melanin particles were observed in the black mantle edge using transmission electron microscope. Magnetic bead binding and Western blot experiments showed that the CgCBP protein can specifically bind to chitin and in vivo RNAi screening indicated that CgCBP knockdown can change the structure of the shell periostracum and reduce its pigmentation. All these results suggest that the outer fold of mantle may have more important roles in shell pigmentation, shell periostracum structure is functionally correlated with shell pigmentation, and the CgCBP gene ultra-highly expressed in the outer fold may influence shell pigmentation by affecting its periostracum structure.