bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetic characterization of pediatric patients with progressive familial intrahepatic cholestasis type 3 (PFIC3): identification of 14 novel ABCB4 variants and review of the literatures
Authors: Chen Rong , Yang Feng-Xia , Tan Yan-Fang , Deng Mei , Li Hua , Xu Yi , Ouyang Wen-Xian , Song Yuan-Zong 
Published: December 2022

Abstract
Background
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients.

Methods
The clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed.

Results
The 13 new PFIC3 patients included six females and seven males, and the main presentations were hepatomegaly, splenomegaly, jaundice, and pruritus, as well as increased levels of gamma-glutamyl transpeptidase (GGT). Fourteen new ABCB4 variants were detected, including eight diagnosed to be likely-pathogenic and six, pathogenic. Among all the 95 PFIC3 cases, hepatomegaly was observed in 85.3% (81/95), pruritus in 67.4% (64/95), splenomegaly in 52.6% (50/95), jaundice in 48.4% (46/95), portal hypertension in 34.7% (33/95) and GGT elevation in 100% (88/88) of the patients. Positive responses at varied degrees to oral ursodeoxycholic acid (UDCA) treatment were observed in 66.1% (39/59) of the patients, among whom 38.5% (15/39) fully recovered in terms of the laboratory changes. Although the condition remained stable in 53 patients (58.9%, 53/90), the clinical outcomes were not promising in the rest 37 cases (41.1%, 37/90), including 7 died, 27 having undergone while another 3 waiting for liver transplantation. A total of 96 ABCB4 variants were detected in the 95 patients. PFIC3 patients with biallelic null variants exhibited earlier onset ages [10.5 (2, 18) vs. 19 (8, 60) months, p = 0.007], lower UDCA response rate [18.2% (2/11) vs. 77.1% (37/48), p = 0.001], and more unpromising clinical outcomes [80% (12/15) vs. 33.3% (25/75), p = 0.001], compared with those with non-biallelic null variants.

Conclusions
PFIC3 presented with hepatomegaly, pruritus, splenomegaly and jaundice with increased serum GGT level as a biochemistry hallmark. Although varying degrees of improvement in response to UDCA therapy were observed, 41.1% of PFIC3 patients exhibited unfavorable prognosis. ABCB4 genotypes of biallelic null variants were associated with severer PFIC3 phenotypes. Moreover, the 14 novel variants in this study expanded the ABCB4 mutation spectrum, and provided novel molecular biomarkers for diagnosis of PFIC3 patients.
Large-scale genomic and transcriptomic profiles of rice hybrids reveal a core mechanism underlying heterosis
Authors: Xie Jianyin , Wang Weiping , Yang Tao , Zhang Quan , Zhang Zhifang , Zhu Xiaoyang , Li Ni , Zhi Linran , Ma Xiaoqian , Zhang Shuyang , Liu Yan , Wang Xueqiang , Li Fengmei , Zhao Yan , Jia Xuewei , Zhou Jieyu , Jiang Ningjia , Li Gangling , Liu Miaosong , Liu Shijin , Li Lin , Zeng An , Du Mengke , Zhang Zhanying , Li Jinjie , Zhang Ziding , Li Zichao , Zhang Hongliang 
Published: December 2022

Abstract
Background
Heterosis is widely used in agriculture. However, its molecular mechanisms are still unclear in plants. Here, we develop, sequence, and record the phenotypes of 418 hybrids from crosses between two testers and 265 rice varieties from a mini-core collection.

Results
Phenotypic analysis shows that heterosis is dependent on genetic backgrounds and environments. By genome-wide association study of 418 hybrids and their parents, we find that nonadditive QTLs are the main genetic contributors to heterosis. We show that nonadditive QTLs are more sensitive to the genetic background and environment than additive ones. Further simulations and experimental analysis support a novel mechanism, homo-insufficiency under insufficient background (HoIIB), underlying heterosis. We propose heterosis in most cases is not due to heterozygote advantage but homozygote disadvantage under the insufficient genetic background.

Conclusion
The HoIIB model elucidates that genetic background insufficiency is the intrinsic mechanism of background dependence, and also the core mechanism of nonadditive effects and heterosis. This model can explain most known hypotheses and phenomena about heterosis, and thus provides a novel theory for hybrid rice breeding in future.
Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design
Authors: Nickerson Peter W. , Böhmig Georg A. , Chadban Steve , Kumar Deepali , Mannon Roslyn B. , van Gelder Teun , Lee James C. , Adler Scott , Chong Edward , Djamali Arjang 
Published: December 2022

Abstract
Background
Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR.

Methods
IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia.

Discussion
IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR.

Trial registration
ClinicalTrials.govNCT03744910. Registered on November 19, 2018.
A comparative study of patient satisfaction about anesthesia with dexmedetomidine for ambulatory dental surgery
Authors: Garip Levin , Verbist Jasmin , Stragier Hendrik , Meyns Joeri , Mesotten Dieter , Vundelinckx Joris 
Published: December 2022

Abstract
Objective
Intranasal administration of dexmedetomidine for monitored anesthesia care (MAC) appears to be an effective, safe, and appropriate alternative to general anesthesia (GA) for ambulatory dental surgery. Based on the available evidence we evaluated a new MAC protocol with intranasal dexmedetomidine as the primary choice.
To assess a difference in patient satisfaction and anesthesia-related discomfort between GA and MAC in ambulatory dental surgery, a study was conducted among patients undergoing various dental procedures. Patient satisfaction and anesthesia-related discomfort were assessed on the first postoperative day using the Bauer patient satisfaction questionnaire.

Results
Although the differences were small, patients in the MAC group were overall more satisfied with the general care compared to the GA group (p < 0.02). Patients in the MAC group reported more postoperative drowsiness compared to the GA group (p < 0.05), but less postoperative hoarseness and sore throat (p = 0.005 and p < 0.001, respectively). Moreover, postoperative thirst was more common in the GA group (p = 0.002).
In conclusion, the differences in patient satisfaction and anesthesia-related discomfort between GA and MAC in this implementation study were small but appeared to favor MAC with intranasal dexmedetomidine over GA as anesthesia method during dental ambulatory surgery.
The rare thoracic complication: perforation of gastric fundus ulcer: a case report
Authors: Polyakov I. S. , Kovalenko A. L. , Petrovsky A. N. , Akobyan A. V. , Porhanov V. A. 
Published: December 2022

Abstract
Background
Gastropleural fistula is an exceptionally rare condition, the incidence of which is currently unknown (Kunieda et al. in Intern Med 51(3):331, 2012, https://doi.org/10.2169/internalmedicine.51.6823, Iqbal et al. in Cureus 11(2):e4136, 2019, https://doi.org/10.7759/cureus.4136, Kathayanatt et al. in Lung India 37(2):174–175, 2020, https://doi.org/10.4103/lungindia.lungindia_242_17). The etiology varies from traumatic or iatrogenic injury to perforation in a herniated stomach due to ischemia, ulceration, or malignancy.

Case presentation
A 27-year-old European male presented to our hospital with complaints of general weakness and shortness of breath. The patient had a single episode of hemoptysis before admission. A computed tomography scan demonstrated a left-sided pyopneumothorax, a defect in the left main bronchus, and signs of pneumonia in the lower sections of the right lung. Therefore, a rare complication of perforation of a gastric fundus ulcer with the formation of a subdiaphragmatic abscess, gastropleural fistula, gangrene of the left lung with circular necrosis of the left main bronchus and diastasis of its edges, and pleural empyema on the left is presented in this report.

Conclusions
Although, a radical surgery may be preferable for this suspected malignancy; it should be weighed carefully against the risk of sepsis and the morbidity associated with a prolonged procedure in a sick patient. Damage-control surgery may be a viable option for a very sick patient, with more extensive resection reserved for later, provided the risk of infection and bleeding has been mitigated.
Some inequalities for cr-log-h-convex functions
Authors: Liu Wei , Shi Fangfang , Ye Guoju , Zhao Dafang 
Published: December 2022

AbstractThe main purpose of this paper is to study certain inequalities forcr-log-h-convex functions with an interval value. To this end, we first give a definition ofcr-log-h-convexity of interval-valued functions under thecr-order and study some properties of such functions. On this basis, we establish the Jensen-, Hermite–Hadamard-, and Fejér-type inequalities forcr-log-h-convex functions, and discuss some special cases. In addition, we give some numerical examples to illustrate the accuracy of the results obtained.
Balancing wind power deployment and sustainability objectives in Swedish planning and permitting
Authors: Wretling Vincent , Balfors Berit , Mörtberg Ulla 
Published: December 2022

Abstract
Background
Wind power is a critical renewable energy technology in efforts to achieve the global climate targets. However, local impacts do occur, which demands careful consideration in planning and permitting. Sweden has set an ambition to triple land-based wind power by 2040, and municipalities play a key role in both the planning and permitting process, due to a planning monopoly and veto power in the permitting process. This calls for an investigation of Swedish wind power governance, with a particular focus on recent trends in municipal wind power planning, how wind power is balanced in relation to sustainability objectives in planning and permitting, and insights from practitioners regarding their capacities and drivers.

Results
The results show that about two-thirds of Swedish municipalities have conducted wind power planning in some form, but this basis for decision-making has become outdated due to a lack of institutional capacity at the municipal level. Secondly, the study finds that many municipalities perceive that there are insufficient incentives for a continued wind power expansion. Lastly, the study sheds light on a large heterogeneity within wind power planning practice concerning how trade-offs between wind power deployment and other sustainability aspects are handled, as well as a lack of coherence between planning and permitting.

Conclusions
It is concluded that the current state of municipal wind power planning raises questions regarding the legitimacy of municipal decision-making in terms of perceived justice among local inhabitants and highlights the need for updated wind power plans. Moreover, to promote local acceptance in the future, formalised financial compensation and strategic initiatives that enable the localisation of electricity-intensive industry within municipalities with large-scale wind power production can be two key components. The results also highlight the need for additional support at the municipal level, including access to critical competence and relevant knowledge to enable trade-offs between the different sustainability considerations in an informed and balanced manner. Finally, regional dialogue with key actors, such as the military, Sami representatives and grid operators, would facilitate the handling of inter-municipal issues, in particular by fostering co-operation regarding inter-municipal wind sites.
A tree-ring record of historical fire activity in a piedmont longleaf pine (Pinus palustris Mill.) woodland in North Carolina, USA
Authors: Rother Monica T. , Patterson Thomas W. , Knapp Paul A. , Mitchell Tyler J. , Allen Nell 
Published: December 2022

Abstract
Background
Longleaf pine (Pinus palustris Mill.) ecosystems were historically widespread in the North American Coastal Plain and in some southeastern piedmont and montane settings. The naval stores industry, deforestation, and other human activities resulted in an extensive loss (c. 97% loss) of the original woodlands and savannas. Longleaf pine ecosystems are maintained by frequent surface fire which promotes successful regeneration and maintains open canopy conditions and a largely herbaceous understory. Fire regimes (including the frequency and seasonality of fire) likely varied across the entire range of longleaf pine and through time; further research is needed to elucidate this variability.

Results
We used fire scars in stumps and snags to reconstruct fire history in a piedmont longleaf pine ecosystem in North Carolina. For each tree sampled, we examined multiple cross sections to avoid omission of fire events recorded by smaller fire scars. Our samples revealed evidence of frequent fire (c. 3–4-year fire interval) beginning in the early eighteenth century and extending to the mid-nineteenth century. Fires occurred in the dormant and early earlywood positions of annual rings and were likely human ignited.

Conclusions
To our knowledge, this is the first tree-ring-based fire history in longleaf pine of the piedmont. As such, it offers a rare glimpse into historical fire activity in a now scarce but important ecological setting. More research is needed to develop additional fire chronologies in the piedmont region, including for longer periods of time and for larger spatial areas.
Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial
Authors: Thieblemont Catherine , Phillips Tycel , Ghesquieres Herve , Cheah Chan Y. , Clausen Michael Roost , Cunningham David , Do Young Rok , Feldman Tatyana , Gasiorowski Robin , Jurczak Wojciech , Kim Tae Min , Lewis David John , van der Poel Marjolein , Poon Michelle Limei , Cota Stirner Mariana , Kilavuz Nurgul , Chiu Christopher , Chen Menghui , Sacchi Mariana , Elliott Brian , Ahmadi Tahamtan , Hutchings Martin , Lugtenburg Pieternella J. 
Published: December 2022

PURPOSE Epcoritamab is a subcutaneously administered CD3xCD20 T-cell–engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. PATIENTS AND METHODS In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037 ), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. RESULTS As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20‐83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell–associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. CONCLUSION Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.
Neoadjuvant Treatment Versus Upfront Surgery in Resectable Pancreatic Cancer: A Cost-Effectiveness Analysis
Authors: Arjani Simran , Prasath Vishnu , Suri Nipun , Li Sharon , Ahlawat Sushil , Chokshi Ravi J. 
Published: December 2022

PURPOSE:Pancreatic cancer (PC) has an overall 5-year survival rate of 10%. The use of neoadjuvant chemoradiation is debated in resectable disease. The purpose of this study is to evaluate the cost-effectiveness of neoadjuvant chemoradiation followed by pancreaticoduodenectomy (NACRT) versus upfront pancreaticoduodenectomy and adjuvant chemotherapy (USR) in resectable PC.METHODS:A decision tree model was used to estimate the cost-effectiveness of NACRT versus USR. Values from the published literature populate the tree: costs from Medicare (FY2021) reimbursements, and morbidity and survival data for quality-adjusted life-years (QALYs). Patients with resectable pancreatic adenocarcinoma who qualified for resection were included. The ICER was the primary outcome. The model was validated using one-way and two‐way deterministic, as well as probabilistic sensitivity analyses.RESULTS:The base case was modeled using a 65-year-old male. NACRT yielded 1.61 QALYs at $45,483.52 USD. USR yielded 1.47 QALYs at a discount of $6,840.96 USD. The ICER was $48,130 USD, which favors NACRT. One-way sensitivity analyses upheld these results except when ≤ 21.0% of NACRT patients proceeded to surgery and when ≤ 85.4% of NACRT patients were resectable at surgery. Two-way sensitivity analyses also favored NACRT except in cases when the proportion of resected disease after NACRT decreased. NACRT was favored in 94.3% of 100,000 random-sampling simulations.CONCLUSION:It is more cost-effective to administer NACRT before surgery for patients with resectable PC. On the basis of sensitivity analyses, USR with adjuvant therapy is only favored if rates of resection and eligibility for resection after NACRT decrease. NACRT should be considered in all patients unless there is an absolute contraindication.
When (Non)Differences Make a Difference: The Roles of Demographic Diversity and Ideological Homogeneity in Overcoming Ideologically Biased Decision Making
Authors: Solomon Brittany C. , Hall Matthew E. K. 
Published: December 2022

Increasing demographic diversity is undoubtedly important and can aid in debiasing decision makers. Yet, the promises of demographic diversity are not always realized due to social integration problems. We consider why and for whom differences combined with homogeneity make a difference for groups in terms of integratively complex thinking and ideological decision making. Although research has shown that decision makers often rely on political biases, that work has not addressed when and why decision-making groups are able to overcome these biases—a pervasive concern in today’s politically polarized social milieu. Drawing on the common in-group identity model and research on integrative complexity, we theorize that demographic diversity ultimately yields less ideological decision making because it prompts integrative complexity; however, demographic diversity only accrues this benefit in the presence of ideological homogeneity. We also reason that the relationship between integrative complexity and reduced ideological decision making emerges for more conservative (versus more liberal) groups. We find support for our expectations using a natural experiment of judges on the U.S. Courts of Appeals. Supplemental analyses indicate that working within a demographically diverse and ideologically homogeneous group also positively predicts integrative complexity in future decision-making groups. Finally, we find that demographic and ideological diversity can substitute for one another, but no additional integrative complexity benefits accrue when both are present. We discuss implications of this research in light of the ongoing conversation about the value of diversity and today’s polarized political climate. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2022.1647 .