bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus
Authors: González-Lama Yago , Ricart Elena , Carpio Daniel , Bastida Guillermo , Ceballos Daniel , Ginard Daniel , Marin-Jimenez Ignacio , Menchen Luis , Muñoz Fernando
Published: January 2024

Background

Despite research, there are still controversial areas in the management of Crohn’s disease (CD).

Objective

To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.

Methods

Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process.

Results

Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator.

Conclusion

This document sought to pull together the best evidence, experts’ opinions, and treating physicians’ attitudes when using anti-TNF therapies in patients with CD.
Regulatory approval of clinical trials: is it time to reinvent the wheel?
Authors: Saleh Mansoor , Sharma Karishma , Shamshudin Aisleen , Obayo Innocent , Gondi Stacey , Karimi Noureen
Published: January 2024

Less than 1% of all clinical trials are conducted in Africa. In 2019, only six of 26 oncology clinical trials conducted in Africa were conducted in countries with subjects of African ancestry. There are multiple barriers that hinder the conduct of cancer clinical trials in Africa. Time to trial activation (TTA) is the administrative and regulatory process required before a study can be activated—an important metric and often a major barrier for site selection. In Kenya, TTA involves review by Institutional Review Board (IRB), Pharmacy and Poisons Board, National Commission for Science, Technology and Innovation and Ministry of Health, all in a sequential fashion. We performed a prospective review of TTA for all clinical trials initiated and began enrolment at the Aga Khan University-Clinical Research Unit between June 2020 and November 2022. TTA was defined as total time from submission of study documents (to regulatory bodies) to site activation by the sponsor. A total of 12 studies were submitted for regulatory review. Eleven (nine industry sponsored and two investigator initiated) were approved for activation. Three were COVID-19-related studies and eight were non-COVID-19-related studies. Mean TTA for COVID-related studies was 80 days (range 40–120). Mean TTA for non-COVID-related studies was 259 days (range 190–399). This TTA difference was statistically significant (p=0.02). TTA remains a significant barrier to the efficient regulatory approval of and subsequent conduct of clinical trials in Africa. COVID-19 pandemic revealed that parallel processing and expedited review of clinical trials allows efficient TTA without compromising human subject safety or data integrity. These lessons need to be applied to all clinical trials in order for African sites to become competitive and contribute data from African patients to global knowledge.
The symptom to assessment pathway for suspected chronic limb-threatening ischaemia (CLTI) affects quality of care: a process mapping exercise
Authors: Atkins Eleanor , Kellar Ian , Birmpili Panagiota , Waton Sam , Li Qiuju , Johal Amundeep S , Boyle Jon R , Pherwani Arun D , Chetter Ian , Cromwell David A
Published: January 2024

Background

Delays in the pathway from first symptom to treatment of chronic limb-threatening ischaemia (CLTI) are associated with worse mortality and limb loss outcomes. This study examined the processes used by vascular services to provide urgent care to patients with suspected CLTI referred from the community.

Methods

Vascular surgery units from various regions in England were invited to participate in a process mapping exercise. Clinical and non-clinical staff at participating units were interviewed, and process maps were created that captured key staff and structures used to create processes for referral receipt, triage and assessment at the units.

Results

Twelve vascular units participated, and process maps were created after interviews with 45 participants. The units offered multiple points of access for urgent referrals from general practitioners and other community clinicians. Triage processes were varied, with units using different mixes of staff (including medical staff, podiatrists and s) and this led to processes of varying speed. The organisation of clinics to provide slots for ‘urgent’ patients was also varied, with some adopting hot clinics, while others used dedicated slots in routine clinics. Service organisation could be further complicated by separate processes for patients with and without diabetes, and because of the organisation of services regionally into vascular networks that had arterial and non-arterial centres.

Conclusions

For referred patients with symptoms of CLTI, the points of access, triage and assessment processes used by vascular units are diverse. This reflects the local context and ingenuity of vascular units but can lead to complex processes. It is likely that benefits might be gained from simplification.
Utility of Goal Attainment Scaling (GAS) in evaluating a multicomponent exercise programme for community-dwelling pre-frail older adults
Authors: Fang Juan , Ren Jianping , Wang Jinjing , Qiu Xiantao , Zhang Shiyan , Yuan Shuang , Wu Liangfeng , Xie Lin , Yu Le
Published: January 2024

Objectives

This study aimed to investigate the effectiveness of Goal Attainment Scaling (GAS) in assessing an intervention for pre-frail senior citizens. Additionally, the study aimed to explain how the GAS goals were established based on the International Classification of Functioning, Disability and Health (ICF) categories, including body function, activity and participation and environmental factors.

Methods

In this study, 220 pre-frail older adults were randomly selected to participate in a controlled trial. The intervention group engaged in multicomponent exercise three times a week, once at a community health service location and twice at home. The control group received advice on physical activity but did not have supervised exercise. Participants in both groups selected individualised GAS goals from 23 goals developed based on ICF by focus group discussion. The study used generalised estimating equations to analyse the differences between the groups.

Results

The study included 144 participants, 72 in the exercise group and 72 in the control group. The top three individualised goals for all participants were vestibular functions (53.5%), pain management (43.1%) and lifting and carrying objects (31.9%). Both groups saw a significant increase in GAS scores at week 8 and week 24 of the intervention (p<0.05), but the exercise group showed a more significant improvement (p<0.05). The participants living alone were associated with lower postintervention improvements in the GAS scores. In contrast, the participants who were using a smartphone were likely to get higher postintervention improvements in the GAS scores.

Conclusions

GAS can be a valuable tool for setting and evaluating individualised and meaningful goals in body functions, activity and participation and environmental factors. The multicomponent exercise interventions can help pre-frail older adults achieve their expected goals as measured by the GAS.
Trauma surgical skill sustainment at the University of Chicago AMEDD Military-Civilian Trauma Team Training Site: an observation report
Authors: Plackett Timothy P , Jaszczak Nicholas , Hampton David A , Prakash Priya , Cone Jennifer , Benjamin Andrew , Rogers Selwyn O , Wilson Kenneth
Published: January 2024

Background

The Army Medical Department (AMEDD) Military-Civilian Trauma Team Training (AMCT3) Program was developed to enhance the trauma competency and capability of the medical force by embedding providers at busy civilian trauma centers. Few reports have been published on the outcomes of this program since its implementation.

Methods

The medical and billing records for the two AMCT3 embedded trauma surgeons at the single medical center were retrospectively reviewed for care provided during August 2021 through July 2022. Abstracted data included tasks met under the Army’s Individual Critical Task List (ICTL) for general surgeons. The Knowledge, Skills, and Abilities (KSA) score was estimated based on previously reported point values for procedures. To assess for successful integration of the embedded surgeons, data were also abstracted for two newly hired civilian trauma surgeons.

Results

The annual clinical activity for the first AMCT3 surgeon included 444 trauma evaluations and 185 operative cases. The operative cases included 80 laparotomies, 15 thoracotomies, and 15 vascular exposures. The operative volume resulted in a KSA score of 21 998 points. The annual clinical activity for the second AMCT3 surgeon included 424 trauma evaluations and 194 operative cases. The operative cases included 92 laparotomies, 8 thoracotomies, and 25 vascular exposures. The operative volume resulted in a KSA score of 22 799 points. The first civilian surgeon’s annual clinical activity included 453 trauma evaluations and 151 operative cases, resulting in a KSA score of 16 738 points. The second civilian surgeon’s annual clinical activity included 206 trauma evaluations and 96 operative cases, resulting in a KSA score of 11 156 points.

Conclusion

The AMCT3 partnership at this single center greatly exceeds the minimum deployment readiness metrics established in the ICTLs and KSAs for deploying general surgeons. The AMEDD experience provided a deployment-relevant case mix with an emphasis on complex vascular injury repairs.
Can stepped collaborative care interventions improve post-traumatic stress disorder symptoms for racial and ethnic minority injury survivors?
Authors: Abu Khadija , Bedard-Gilligan Michelle , Moodliar Rddhi , Bulger Eileen M , Hernandez Alexandra , Knutzen Tanya , Shoyer Jake , Birk Navneet , Conde Cristina , Engstrom Allison , Ryan Paige , Wang Jin , Russo Joan , Zatzick Douglas F
Published: January 2024

Objectives

No large-scale randomized clinical trial investigations have evaluated the potential differential effectiveness of early interventions for post-traumatic stress disorder (PTSD) among injured patients from racial and ethnic minority backgrounds. The current investigation assessed whether a stepped collaborative care intervention trial conducted at 25 level I trauma centers differentially improved PTSD symptoms for racial and ethnic minority injury survivors.

Methods

The investigation was a secondary analysis of a stepped wedge cluster randomized clinical trial. Patients endorsing high levels of distress on the PTSD Checklist (PCL-C) were randomized to enhanced usual care control or intervention conditions. Three hundred and fifty patients of the 635 randomized (55%) were from non-white and/or Hispanic backgrounds. The intervention included care management, cognitive behavioral therapy elements and, psychopharmacology addressing PTSD symptoms. The primary study outcome was PTSD symptoms assessed with the PCL-C at 3, 6, and 12 months postinjury. Mixed model regression analyses compared treatment effects for intervention and control group patients from non-white/Hispanic versus white/non-Hispanic backgrounds.

Results

The investigation attained between 75% and 80% 3-month to 12-month follow-up. The intervention, on average, required 122 min (SD=132 min). Mixed model regression analyses revealed significant changes in PCL-C scores for non-white/Hispanic intervention patients at 6 months (adjusted difference −3.72 (95% CI −7.33 to –0.10) Effect Size =0.25, p<0.05) after the injury event. No significant differences were observed for white/non-Hispanic patients at the 6-month time point (adjusted difference −1.29 (95% CI −4.89 to 2.31) ES=0.10, p=ns).

Conclusion

In this secondary analysis, a brief stepped collaborative care intervention was associated with greater 6-month reductions in PTSD symptoms for non-white/Hispanic patients when compared with white/non-Hispanic patients. If replicated, these findings could serve to inform future American College of Surgeon Committee on Trauma requirements for screening, intervention, and referral for PTSD and comorbidities.

Level of evidence

Level II, secondary analysis of randomized clinical trial data reporting a significant difference.

Trial registration number

NCT02655354.
AMY Lorentz invariant parton cascade: the thermal equilibrium case
Authors: Kurkela Aleksi , Törnkvist Robin , Zapp Korinna
Published: January 2024

We introduce the parton cascade Alpaca, which evolves parton ensembles corresponding to single events according to the effective kinetic theory of QCD at high temperature formulated by Arnold, Moore and Yaffe by explicitly simulating elastic scattering, splitting and merging. By taking the ensemble average over many events the phase space density (as evolved by the Boltzmann equation) is recovered, but the parton cascade can go beyond the evolution of the mean because it can be turned into a complete event generator that produces fully exclusive final states including fluctuations and correlations. The parton cascade does not require the phase space density as input (except for the initial condition at the starting time). Rather, effective masses and temperature, which are functions of time and are defined as integrals over expressions involving the distribution function, are estimated in each event from just the parton ensemble of that event. We validate the framework by showing that ensembles sampled from a thermal distribution stay in thermal equilibrium even after running the simulation for a long time. This is a non-trivial result, because it requires all parts of the simulation to intertwine correctly.
Blockchain-Assisted Access Control with Shuffled Shepherd Fire Hawk Optimisation-Key Generation for Privacy Protection in Cloud
Authors: Gutte Vitthal Sadashiv , Hande Yogita , Deokate Sarika Tanaji , Bhosale Poonam Chandrakant , Kulkarni Yogesh R.
Published: January 2024

Cloud is a model of computing providing on-demand availability of computer system resources, mainly data storage and computing power, without the user’s active management. This provides sharing and reduces user computing and storage costs. With the development of cloud scale and intensification, cloud security is becoming a vital issue in the cloud computing field. Here, a newly optimised hybridisation algorithm, namely, Shuffled Shepherd Fire Hawk Optimization (SSFHO) algorithm is proposed for key generation to initiate privacy protection in the cloud. The different entities involved in this approach are Data Owner (DO), Data User (DU), blockchain, and Cloud Service Provider (CSP). Here, the access control process includes seven categories, such as initialisation, registration, generation of key, data access control, authorisation, authorisation revocation and data protection. Also, registration is done in three phases, like registration of cloud, registration of user and resource publishing. Moreover, SSFHO is the integration among Shuffled Shepherd Optimization Algorithm (SSOA) and Fire Hawk Optimization (FHO) algorithm. The performance of the model is done with various performance metrics like, authorisation time, privacy rate, and memory. These revealed high values of privacy rate of 0.93, low values of authorisation time and memory of 0.559 and 0.843 GHz.
Max Weight Independent Set in Graphs with No Long Claws: An Analog of the Gyárfás’ Path Argument
Authors: Majewski Konrad , Masařík Tomáš , Masaříková Jana , Okrasa Karolina , Pilipczuk Marcin , Rzążewski Paweł , Sokołowski Marek
Published: January 2024

We revisit recent developments for the
Maximum Weight Independent Set
problem in graphs excluding a subdivided claw
S

t,t,t

as an induced subgraph and provide a subexponential-time algorithm with improved running time

\(2^{\mathcal {O}(\sqrt {nt}\log n)}\)

and a quasipolynomial-time approximation scheme with improved running time

\(2^{\mathcal {O}(\varepsilon ^{-1}t \log ^{5} n)}\)

.

The Gyárfás’ path argument, a powerful tool that is the main building block for many algorithms in
P

t

-free graphs, ensures that given an
n
-vertex
P

t

-free graph, in polynomial time we can find a set
P
of at most
t
-1 vertices such that every connected component of
G-N[P]
has at most
n
/2 vertices. Our main technical contribution is an analog of this result for
S

t,t,t

-free graphs: given an
n
-vertex
S

t,t,t

-free graph, in polynomial time we can find a set
P
of

\(\mathcal {O}(t \log n)\)

vertices and an extended strip decomposition (an appropriate analog of the decomposition into connected components) of
G-N[P]
such that every particle (an appropriate analog of a connected component to recurse on) of the said extended strip decomposition has at most
n
/2 vertices.
Blockchain-based Decentralized Reward Sharing: The Case of Mining Pools
Authors: Gudmundsson Jens , Hougaard Jens Leth
Published: January 2024

We introduce a
reciprocity protocol
, an innovative approach to coordinating and sharing rewards in blockchains. Inherently decentralized and implementable, it puts emphasis on incentives rather than forcing specific sharing rules from the outset. Analyzing the non-cooperative game the protocol induces, we identify a robust, strict, and Pareto-dominant symmetric equilibrium. In it, even self-centered participants show extensive systemic reciprocity. Thus, despite a setting that is generally unfavorable to reciprocal behavior, the protocol enables users to build trust between themselves by taking on a role akin to a social contract.
Are Professional Skills Learnable? Beliefs and Expectations Among Computing Graduates
Authors: Cortázar Catalina , Goñi Iñaki , Ortiz Andrea , Nussbaum Miguel
Published: January 2024

Integrating graduate education with professional skills development is still a challenge. People's beliefs about learning impact their learning processes. Therefore, we need to understand the mindset of graduates to determine best practices for promoting professional skills development. In this study, we explore the perspective of computing graduates within an Engineering educational program. This study aims to answer the following research questions: Which skills do computing graduates perceive they need in the workplace, and how do they position themselves regarding these skills? What learning beliefs do computing graduates hold regarding the skills required in the workplace? The research team conducted semistructured interviews with computing graduates within an Engineering program to analyze their experiences. The interviews were analyzed using grounded theory. As a result, the participants viewed professional and technical skills as independent, with professional skills perceived as more relevant to work success. The participants considered themselves to possess these skills. Our findings identify four learning beliefs within a fixed and growth mindset: (1) An essential personal characteristic that context may influence; (2) a learning outcome determined by early experiences; (3) a learning process associated with informal learning experiences; and (4) a learning process associated with formal learning experiences. We acknowledge the differences in perception between alums and the industry regarding possessing essential professional skills. We also highlight the need to position these skills as learnable during lectures contributing to Computing and Engineering Education.
Collaborative Inversion of Soil Water Content in Alpine Meadow Area Based on Multitemporal Polarimetric SAR and Optical Remote Sensing Data
Authors: Kong Meng , Zuo Xiaoqing , Li Yongfa
Published: January 2024

Soil water content is a critical environmental parameter in research and practice, though various technological and contextual constraints limit its estimation in arid areas with vegetation cover. This study combined the multitemporal remote sensing data of Sentinel-1 and Landsat 8 to conduct an inversion study on surface soil water content under low vegetation cover in Nagqu, central Tibetan Plateau. Four vegetation indices (NDVI, ARVI, EVI, and RVI) were extracted from optical remote sensing data. A water cloud model was used to eliminate the influence of the vegetation layer on the backscattering coefficient associated with vegetation cover, and a predictive model suitable for the Nagqu area was constructed. The water cloud model effectively incorporated a vegetation index instead of vegetation water content. We found that VV polarization was more suitable for soil water content inversion than VH polarization. Among the four vegetation indices, the soil water content inversion model constructed with RVI under VV polarization had the best fit (R2 = 0.8212; RMSE = 6.30). The second-best fit was observed for vegetation water content-NDVI (R2 = 0.8201). The soil water content inversion models all had an R2 > 0.6, regardless of the vegetation index used, though the RVI had the best fitting effect, indicating that this vegetation index is highly applicable in the water cloud model, as a substitute for vegetation water content, and is expected to perform well in similar study sites.
Long-Term Surgical Outcomes of Glaucoma Drainage Implants in Eyes with Preoperative Intraocular Pressure Less than 19 mmHg
Authors: Hallaj Shahin , Wong Jae-Chiang , Hock Lauren E. , Kolomeyer Natasha Nayak , Shukla Aakriti G. , Pro Michael J. , Moster Marlene R. , Myers Jonathan S. , Razeghinejad Reza , Lee Daniel
Published: January 2024

Background. This retrospective review reports on patients who underwent glaucoma drainage implant (GDI) surgery and had baseline intraocular pressure (IOP) of ≤18 mmHg with at least one year of follow-up. Methods. Clinical data of 67 eyes of 67 patients were collected from patients’ charts, and the outcomes of GDI were evaluated until 7 years. GDI failure was defined as IOP reduction of less than 20% from the baseline at two consecutive visits three months after surgery, decline to no light perception, or if additional glaucoma surgery was performed. Results. The average age was 65.9 ± 13.2 years. Most cases were male (52.2%), White (53.7%), and had primary open-angle glaucoma (62.7%). Forty-four eyes had prior glaucoma surgery (68.6%) and 46 (68.6%) had severe glaucoma. Though postoperative (postop) IOP changes were insignificant, the average postop number of medications dropped from 2.4 ± 1.4 to 1.9 ± 1.2 medications two years after surgery (p=0.0451). Postop complications (23.9%) included GDI exposure (7.5%), inflammation (4.5%), shallow anterior chamber (4.5%), and strabismus (1.5%). Hypotony was observed in 4 eyes (5.9%), none of which developed hypotony maculopathy. The cumulative one-year failure rate was 56.7%, most of which were due to failure to lower IOP. Conclusion. In patients with baseline IOP ≤18 mmHg who had GDI surgery, though the change in IOP was not statistically significant, the number of medications dropped and visual field progression slowed in a subset of patients with adequate perimetric data. Due to a relatively high rate of complications and limited effectiveness in lowering IOP, GDI should be cautiously used in these eyes.
Numerical and Scientific Investigation of Some Molecular Structures Based on the Criterion of Super Classical Average Assignments
Authors: Rajesh Kannan A. , Alessa Nazek , Loganathan K. , Pattanaik Balachandra
Published: January 2024

Numbering a graph is a very practical and effective technique in science and engineering. Numerous graph assignment techniques, including distance-based labeling, topological indices, and spectral graph theory, can be used to investigate molecule structures. Consider the graph G, with the injection Ω from the node set to 1,2,…,∆, where ∆ is the sum of the number of nodes and links. Assume that the induced link assignment Ω∗ is the ceiling function of the average of root square, harmonic, geometric, and arithmetic means of the vertex labels of the end vertices of each edge. If the union of range of Ω of the node set and the range of

Ω

of the link set is the set 1,2,…,∆, then Ω is called a super classical average assignment (SCAA). This is known as the SCAA criterion. In this study, the graphical structures corresponding to chemical structures based on the SCAA criterion are demonstrated. The graphical depiction of chemical substances was first defined and second, the union of any number of cycles Cn, the tadpole graph, the graph extracted by identifying a line of any two cycles Cm and Cn, and the graph extracted by joining any two cycles by a path are all examined in this work.
A Novel Antenna Design of Compact HF and UHF Passive RFID Tags with Interconnected Structure for Energy Harvesting and Tracking Systems
Authors: Kawdungta Supakit , Mhunkaew Theerayut , Torrungrueng Danai , Chou Hsi-Tseng
Published: January 2024

We propose a new dual-band passive RFID tag antenna design by combining a rectangular spiral coil and patch-meander-line dipole with an interconnected structure. This design enables operation in high-frequency (HF) and ultra-high-frequency (UHF) RFID systems, suitable for energy harvesting and tracking applications. The simulations by the CST full-wave software demonstrate conjugate impedance matching between the tag antenna and two RFID tag chips. At 13.56 MHz (HF), the tag antenna exhibits an inductive reactance of 422.79 Ω, while at 922.5 MHz (UHF), it presents an impedance of 9.41+j174.96 Ω. The antenna generates a maximum magnetic field intensity of 0.5 A/m and omnidirectional electromagnetic fields with an antenna realized gain of -4.26 dBi at 922.5 MHz. We also analyze the impact of the tag antenna combination using numerical software. Furthermore, we fabricate a prototype tag antenna and validate its performance with RFID readers. The proposed tag antenna achieves the maximum read ranges of 11 cm and 6.9 m for the HF (13.56 MHz) and UHF (920-925 MHz) bands, respectively, accompanied by the energy harvesting of 1.48 volts at the HF band by the coupling magnetic field received by the HF antenna to the chip ST25DV04K at the output voltage pin.
Data from RETRACTED: miRNA-302b Suppresses Human Hepatocellular Carcinoma by Targeting AKT2
Authors: Wang Lumin , Yao Jiayi , Zhang Xiaogang , Guo Bo , Le Xiaofeng , Cubberly Mark , Li Zongfang , Nan Kejun , Song Tusheng , Huang Chen
Published: January 2024

Abstract
miRNAs (miR) play a critical role in human cancers, including hepatocellular carcinoma. Although miR-302b has been suggested to function as a tumor repressor in other cancers, its role in hepatocellular carcinoma is unknown. This study investigated the expression and functional role of miR-302b in human hepatocellular carcinoma. The expression level of miR-302b is dramatically decreased in clinical hepatocellular carcinoma specimens, as compared with their respective nonneoplastic counterparts, and in hepatocellular carcinoma cell lines. Overexpression of miR-302b suppressed hepatocellular carcinoma cell proliferation and G1–S transition in vitro, whereas inhibition of miR-302b promoted hepatocellular carcinoma cell proliferation and G1–S transition. Using a luciferase reporter assay, AKT2 was determined to be a direct target of miR-302b. Subsequent investigation revealed that miR-302b expression was inversely correlated with AKT2 expression in hepatocellular carcinoma tissue samples. Importantly, silencing AKT2 recapitulated the cellular and molecular effects seen upon miR-302b overexpression, which included inhibiting hepatocellular carcinoma cell proliferation, suppressing G1 regulators (Cyclin A, Cyclin D1, CDK2) and increasing p27Kip1 phosphorylation at Ser10. Restoration of AKT2 counteracted the effects of miR-302b expression. Moreover, miR-302b was able to repress tumor growth of hepatocellular carcinoma cells in vivo.

Implications: Taken together, miR-302b inhibits HCC cell proliferation and growth in vitro and in vivo by targeting AKT2. Mol Cancer Res; 12(2); 190–202. ©2013 AACR.
EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas
Authors: DuCote Tanner J. , Song Xiulong , Naughton Kassandra J. , Chen Fan , Plaugher Daniel R. , Childress Avery R. , Gellert Abigail R. , Skaggs Erika M. , Qu Xufeng , Liu Jinze , Liu Jinpeng , Li Fei , Wong Kwok-Kin , Brainson Christine F.
Published: January 2024

Two important factors that contribute to resistance to immune checkpoint inhibitors (ICI) are an immune-suppressive microenvironment and limited antigen presentation by tumor cells. In this study, we examine whether inhibition of the methyltransferase enhancer of zeste homolog 2 (EZH2) can increase ICI response in lung squamous cell carcinomas (LSCC). Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. Chromatin immunoprecipitation sequencing confirmed loss of EZH2-mediated histone marks and gain of activating histone marks at key loci. Furthermore, we demonstrate strong tumor control in models of both autochthonous and syngeneic LSCC treated with anti-PD1 immunotherapy with EZH2 inhibition. Single-cell RNA sequencing and immune cell profiling demonstrated phenotypic changes toward more tumor suppressive phenotypes in EZH2 inhibitor–treated tumors. These results indicate that EZH2 inhibitors could increase ICI responses in patients undergoing treatment for LSCC.

Significance:

The data described here show that inhibition of the epigenetic enzyme EZH2 allows derepression of multiple immunogenicity factors in LSCC, and that EZH2 inhibition alters myeloid cells in vivo. These data support clinical translation of this combination therapy for treatment of this deadly tumor type.
Rifaximin Treatment of Collagenous Colitis: A Randomised, Double-Blind, Placebo-Controlled Trial
Authors: Becker Sabine , Grode Louise B. , Bonderup Ole K.
Published: January 2024

Introduction: Collagenous colitis (CC) is a disabling disease primarily affecting elderly women. Sparse, well-documented treatment modalities exist, except for budesonide. Long-term and repetitive treatment with budesonide is often necessary. Rifaximin is a poorly absorbed antibiotic with a positive modulatory effect on gut microbiota. In this randomised, double-blind, placebo-controlled single-centre trial, we test the effect of adding rifaximin in continuation to budesonide on relapse rates in CC. Methods: Eligible patients with active, biopsy-verified CC received oral budesonide during a 6-week open-label induction phase. Patients in clinical remission after 4 weeks of treatment were randomised to receive either rifaximin or placebo for 4 weeks. Results: Fifteen patients were randomised to receive either rifaximin (n = 7) or placebo (n = 8). At 12-week follow-up, 2 patients in the rifaximin group were still in remission and none in the placebo group (p = 0.2). The median number of days in remission in the rifaximin group was 42 (interquartile range [IQR] 33–126) compared to 18.5 (IQR 10.5–51.5) in the placebo group (p = 0.189). At 12-week follow-up, the relapse rate per 100 person-days in the placebo group was higher (3.25 [1.40–6.41]) than in the rifaximin group (1.33 [0.43–3.10]). Conclusion: Although not statistically significant (p = 0.0996), the study suggests a potential improvement in relapse rates within the rifaximin group compared to the placebo group. A major limitation in the study is the small sample size.
Analysis of Factors Associated with Constipation in the Population with Obesity: Evidence from the National Health and Nutrition Examination Survey
Authors: Hong Yongping , Chen Xingxing , Liu Junping
Published: January 2024

Introduction: Obesity and constipation are both global problems, but the factors associated with constipation in individuals with obesity are currently understudied. The aim of our study was to explore the factors associated with constipation in people with obesity. Methods: From three cycles of the National Health and Nutrition Examination Survey (NHANES) 2005–2010, data from 14,048 persons aged ≥20 years were collected. Variables included demographics, lifestyle, comorbidities, and dietary data. Multiple logistic regression analysis was used to calculate adjusted prevalence odds ratio (OR) and assess the relationship between different variables and constipation in population with obesity. Results: Using stool consistency definition, multivariate analysis revealed that education ≥12th grade (OR: 0.456; 95% CI: 0.300, 0.694; p = 0.00024), hypertension (OR: 0.505; 95% CI: 0.334, 0.763; p = 0.00119), polypharmacy (OR: 1.669; 95% CI: 1.104, 2.521; p = 0.01507), high cholesterol (OR: 0.400; 95% CI: 0.213, 0.750; p = 0.00430), and high dietary fiber (OR: 0.454; 95% CI: 0.245, 0.841; p = 0.01206) were substantially linked with constipation in the population with obesity. For constipation defined using stool frequency, multivariate regression analysis show constipation in people with obesity had a significant association with the female sex (OR: 2.684; 95% CI: 1.379, 5.223; p = 0.00366 multivariate), Mexican American (OR: 0.142; 95% CI, 0.033, 0.616; p = 0.00914 multivariate), hypertension (OR: 0.569; 95% CI: 0.324, 0.998; p = 0.04916), depression (OR: 2.280; 95% CI: 1.240, 4.195; p = 0.00803), occasional/often milk consumption (OR: 0.473; 95% CI: 0.286, 0.782; p = 0.00356), medium energy (OR: 0.318; 95% CI: 0.118, 0.856; p = 0.02338), polypharmacy (OR: 1.939; 95% CI: 1.115, 3.373; p = 0.01907), and medium moisture (OR: 0.534; 95% CI: 0.285, 0.999; p = 0.04959). In nonobese people, constipation was significantly associated with the female sex and high moisture but not with hypertension and polypharmacy. Conclusion: This study suggests that the population with obesity has many factors that affect constipation such as hypertension, polypharmacy, cholesterol, dietary fiber, depression, and so on, of which hypertension and polypharmacy were significant associated with constipation, regardless of definitions of constipation. Notably, hypertension might be associated with a reduced risk of constipation in people with obesity.
Triglycerides Mediate the Influence of Body Mass Index on Non-Alcoholic Fatty Liver Disease in a Non-Obese Chinese Population with Normal Low-Density Lipoprotein Cholesterol Levels
Authors: Han Xixi , Kong Jingwen , Zhang Hemin , Zhao Yuan , Zheng Yafeng , Wei Chao
Published: January 2024

Introduction: Over 25% of the world’s population has non-obese or lean non-alcoholic fatty liver disease (NAFLD), and the prevalence is higher than average in Asia. The present study focused on the relationship between body mass index (BMI) and non-obese NAFLD in non-overweight people in China, particularly the influence of triglycerides (TG) in the pathogenesis of non-obese NAFLD. The findings suggest new treatments for NAFLD patients with normal BMI, as well as provide an early warning system for the understanding and prevention of NAFLD in non-obese patients. Methods: This cross-sectional study enrolled 159,959 Chinese subjects with BMI <24 kg/m2 and normal levels of low-density lipoprotein cholesterol (LDL-c). The average age was 40.21 ± 13.88 years, and males accounted for 45.7%. A total of 15,907 (9.94%) patients with NAFLD were diagnosed by ultrasonography. Biochemical indicators were measured using an automated analyzer (Abbott AxSYM). The BMI (kg/m2) was calculated from the weight (kg)/height in square meters (m2). The BMI quartile was used as the column-stratified variable to determine the baseline distribution, and logistic regression analysis was used to assess the relationship between NAFLD and its risk factors, with multiple logistic regression used to assess the relationships between BMI or TG and NAFLD and multivariate linear regression used to analyze the association between BMI and TG, while mediation analysis was used to assess the mediation effect of TG. Results: After adjustment of all covariates, the odds ratios were 1.788 (95% CI: 1.749–1.829; p < 0.00001) and 1.491 (95% CI: 1.451–1.532; p < 0.00001) for the association between BMI and TG with NAFLD incidence. The multivariate linear regression coefficient of BMI and TG was β = 0.027 (95% CI: 0.023–0.030; p < 0.00001). Mediation analysis showed that BMI contributed to 10.81% of lean NAFLD with a mediation effect of 2.98%. Conclusion: In a Chinese population with BMI <24 kg/m2 and normal LDL-c levels, BMI and TG were found to be independent predictors of NAFLD. The direct effect of BMI on non-obese NAFLD was 10.41%. The TG level was found to partially mediate the association.
Fighter Pilot Syndrome: A Bow Hunter Syndrome Variant Identified With Dynamic Cerebral Angiography
Authors: Choi Joo Won , Jin Kirsten , Wilson Jessica N. , Pham Andrew , Mehta Tej I. , Tsappidi Samuel , Zhang Jonathan Y. , Hui Ferdinand K. , Brown Stacy C.
Published: January 2024

Background

Dynamic compression of extracranial arteries in the cervicocerebral circulation is a rare phenomenon of ischemic stroke.

Methods

Retrospective chart review.

Results

Here, we present a young fighter pilot who presented with recurrent embolic strokes of undetermined source. He endorsed flying fighter jets for 6 years, during which he was subject to high G‐force loads and extensive in‐flight head maneuvers. Extensive workup identified dynamic arterial compression of his right vertebral artery, which entered the transverse foramen at the C4 level. Dynamic cerebral angiography was used to reveal the specific vessel location and provocative maneuver leading to dynamic occlusion of his right vertebral artery.

Conclusion

This case highlights the utility of dynamic cerebral angiography in identifying previously unexplored causes of arteriogenic emboli formation, particularly in patients with predisposing anatomic and clinical risk factors.
Impact of anti-gravity muscle training protocol on plantar pressure, pain threshold and foot posture on chronic painful heel: an RCT study
Authors: Gotecha S. , Gurudut P. , Welling A. , Kage V.
Published: January 2024

Chronic painful heel (CPH) is a symptom of an underlying condition caused due to obesity, excessive foot pronation, tightness of Tendo-Achilles (TA), excessive running, and sedentary life. The antigravity muscles (AGM) atrophy results due to long working hours in sitting, leading to their deteriorating relationship with gravity thereby reduced sensitivity to its force. Hence, need arises to explore training effects of AGM protocol on CPH condition. A randomised controlled trial was conducted on thirty individuals with CPH allocated randomly to two study groups viz. AGMT (n = 15) and Control group (n = 15) who received intervention for twelve sessions over four weeks. Control group received conventional physiotherapy in form of therapeutic ultrasound and exercises while AGMT received conventional physiotherapy using the AGMT protocol. Outcomes assessed were plantar pressure and foot posture assessed using Harris mat, muscle strength by dynamometer, pain threshold with pressure algometer, and foot functions using Foot and Ankle Ability Measure Scale (FAAM) which were taken at pre- and post-training. The between group analysis of data revealed that foot posture, plantar pressure and muscle strength, pain threshold were significantly better in the AGMT group than in the Control group ( 0.0001), while pain intensity (P = 0.3952) and foot functions (P = 0.2372) were equally effective in both the study groups. In conclusion, the AGMT protocol along with conventional physiotherapy proved to be a promising training protocol for individuals with CPH showing positive outcomes in comparison to conventional therapy alone, suggesting to incorporate AGM strengthening alongside conventional therapy to obtain better clinical outcomes.

Trial registration: This trial was prospectively registered in the Clinical trial registry of India with registration number CTRI/2022/10/046138.
Was There a Resistance Fascism?
Authors: Rodrigo Javier , Pubill Joan
Published: January 2024

Is it possible to identify traces of dissent or even resistance to Francoism within a single fascist party? Can there be elements of radical opposition within fascism in its long duration? This article’s discussion of this question, centered on the Spanish Falange’s case, will focus on two main topics that define the parameters of historiographical discussion of an idealized (‘authentic’, ‘pure’, ‘uncontaminated’, ‘rebellious’) fascism that may also be useful for interpreting and establishing comparisons with other contexts. The first of these topics is the mythification of fascism’s original authenticity and the second is the preeminence of Franco’s providentialist leadership and how it explicitly demonstrates his de facto importance in the construction of the dictatorial regime as a fascist regime through the exercise of power.
“Searching for Meanings and Becoming Better Moms”
Authors: Lin Hsien-Ming
Published: January 2024

This article explores the education-related experiences of Vietnamese immigrant women in Taiwan. The author adopts a qualitative methodology, utilizing semi-structured interviews, followed by a constant comparative analysis. Three core themes are unearthed: the participants’ learning experiences, the process of meaning-making, and the multidimensional impacts of their education. Key findings include the effort invested by participants in obtaining familial support to pursue their education and the learning challenges posed by language barriers. Furthermore, the pursuit of education is found to extend to deeper aspects of self-identity, encompassing motherhood and empowerment. This article illustrates how higher education can facilitate better employment and enhance societal integration and intra-familial power dynamics for immigrant women. Its impact is not unilateral but spans multiple dimensions of their lives in their host society. The insights gained from this article indicate a need for broader, comparative, and diverse research to understand experiences across other immigrant communities in Taiwan.
A problematic species complex of Lasioglossum subgeneric diagnostics in North America (Hymenoptera: Halictidae)
Authors: HETTIARACHCHI THILINA , GIBBS JASON
Published: January 2024

A problematic species complex within Lasioglossum subgenus Sphecodogastra with unusual metallic reflections on the mesosoma is described from North America. Three new species in this complex are described and illustrated: Lasioglossum (Sphecodogastra) iridescens sp. nov., Lasioglossum (Sphecodogastra) dilisena sp. nov., and Lasioglossum (Sphecodogastra) silveirai sp. nov. Our study addresses the challenge of diagnosing Lasioglossum subgenera within North America. We present an updated key for the North American Lasioglossum subgenera.
A Dynamics-Weighted Principal Components Analysis of Dominant Atmospheric Drivers of Ocean Variability with an Application to the North Atlantic Subpolar Gyre
Authors: Amrhein Daniel E. , Stephenson Dafydd , Thompson LuAnne
Published: January 2024

This paper describes a framework for identifying dominant atmospheric drivers of ocean variability. The method combines statistics of atmosphere–ocean fluxes with physics from an ocean general circulation model to derive atmospheric patterns optimized to excite variability in a specified ocean quantity of interest. We first derive the method as a weighted principal components analysis and illustrate its capabilities in a toy problem. Next, we apply our analysis to the problem of interannual upper ocean heat content (HC) variability in the North Atlantic Subpolar Gyre (SPG) using the adjoint of the MITgcm and atmosphere–ocean fluxes from the ECCOv4-r4 state estimate. An unweighted principal components analysis reveals that North Atlantic heat and momentum fluxes in ECCOv4-r4 have a range of spatiotemporal patterns. By contrast, dynamics-weighted principal components analysis collapses the space of these patterns onto a small subset—principally associated with the North Atlantic Oscillation—that dominates interannual SPG HC variance. By perturbing the ECCOv4-r4 state estimate, we illustrate the pathways along which variability propagates from the atmosphere to the ocean in a nonlinear ocean model. This technique is applicable across a range of problems across Earth system components, including in the absence of a model adjoint.

Significance Statement

While the oceans have absorbed 90% of the excess heat associated with human-forced climate change, the change in the ocean’s heat content is not steady, with peaks and troughs superimposed upon a general increase. These fluctuations come from chaotic changes in the atmosphere and ocean and can be hard to disentangle. We use this case of ocean heat content variability to introduce a new method for determining the patterns of weather and climate in the atmosphere that are most effective at generating fluctuations in the ocean. To do this, we combine the statistics of recent atmospheric activity with output from a state-of-the-art numerical ocean model that reveals physical processes driving changes in ocean quantities including ocean heat content. This approach suggests that the atmospheric patterns that stimulate the most energetic changes in ocean heat content in the northern North Atlantic are not necessarily the most energetic patterns present in the atmosphere. We test our findings by preventing these patterns from affecting the ocean in our numerical model and measure a strong reduction in ocean heat content fluctuations.
Fostering Asian American Emerging Adults’ Advocacy Against Anti-Black Racism Through Digital Storytelling
Authors: Keum Brian TaeHyuk , Nguyen Mary Minh Giao , Ahn Lydia HaRim , Wong Michele J. , Wong Lianne J. , Miller Matthew J.
Published: January 2024

We tested whether a digital storytelling video on anti-Black racism could improve empathic reactions to anti-Black racism and decrease fear of Black individuals (FBI) among Asian American emerging adults, and whether these changes were associated with greater anti-racism advocacy intentions. Asian American emerging adults ( Mage = 19.92; N = 205) were randomly assigned to view either storytelling or informational online videos. Data was collected before and after viewing the videos. The changes in empathic reactions and fear were analyzed using polynomial regression with response surface analysis. Those who viewed the storytelling video significantly increased their empathy and this change was significantly associated with greater individual anti-racism advocacy (IndAdv) and institutional anti-racism advocacy (IntAdv). Reductions in fear were not associated with greater advocacy. The informational video did not improve empathy but did decrease fear, which was associated with greater IndAdv. Therefore, digital storytelling videos may be a useful tool to promote advocacy against anti-Black racism.