bluuebunny/crossref_metadata_2025 huggingface dataset:
Rebel Taxation as Extortion or a Technology of Governance? Telling the Difference in India’s Northeast
Authors: Mampilly Zachariah , Thakur Shalaka
Published: March 2024

Payments made to non-state armed groups are often treated as predation. But rebel organizations deploy multiple logics when constructing their taxation systems, many of which cannot be reduced to extortion. Rebels also use taxation as a “technology of governance” to resolve a number of social and political challenges related to constructing a wartime order. Drawing on extensive subnational research in four distinct areas of control by a single organization, the National Socialist Council of Nagaland-Isak Muivah, we argue that two factors, political legitimacy and military control, determine whether taxes are extortive or deployed as a technology of governance. Our controlled comparison shows that rebels frequently implement a wider variety of taxes than commonly presumed and that these different categories of taxation are shaped by the larger social and political context in which the group operates.
Concomitant interventions in mitral valve surgery – A European perspective
Authors: Naruka Vinci , Arjomandi Rad Arian , Chacko Jacob , Liu Guiqing , Afoke Jonathan , Punjabi Prakash P
Published: March 2024

Introduction

In recent years, major findings on concomitant procedures and anticoagulation management have occurred in Mitral Valve (MV) surgery. Therefore, we sought to evaluate the current practices in MV interventions across Europe.

Methods

In October 2021, all national cardio-thoracic societies in the European region were identified following an electronic search and sent an online survey of 14 questions to distribute among their member consultant/attending cardiac surgeons.

Results

The survey was completed by 91 consultant/attending cardiac surgeons across 12 European countries, with 78% indicating MV repair as their specialty area. 57.1% performed >150 operations/year and 71.4% had 10+ years of experience. Concomitant tricuspid valve repair is performed for moderate tricuspid regurgitation (TR) by 69% of surgeons and for mild TR by 26.3%, both with annular diameter >40 mm. 50.6% indicated ischaemic MV surgery in patients undergoing CABG if moderate mitral regurgitation with ERO >20 mm2 and regurgitant volume >30 mL, and 45.1% perform it if severe MR with ERO >40 mm2 and regurgitant volume >60 mL. For these patients the preferred management was: MVR if predictors of repair failure identified (47.2%) and downsizing annuloplasty ring only (34.1%). For atrial fibrillation (AF) in cardiac surgery, 34.1% perform ablation with biatrial lesion and 20% with left sided only. 62.6% perform concomitant Left Atrial Appendage (LAA) Occlusion irrespective of AF ablation with a left atrial clip. A wide variability in anticoagulation strategies for MV repair and bioprosthetic MV valve was reported both for patients in sinus rhythm and AF.

Conclusion

These results demonstrate a variable practice for MV surgery, and a degree of lack of compliance with surgical intervention guidelines and anticoagulation strategy.
The law and policy of library development: A legal text analysis of Indonesian library bills
Authors: Ali Irhamni , Ryan Sarah E.
Published: March 2024

The Indonesian constitution provides for welfare and education. To achieve these constitutional mandates, the Indonesian government passed several laws as the foundation for lifelong education, including the Library Act of 2007 and the National Repository Act of 2018. These Acts are the main legal foundation for the National Library of Indonesia (NLI) to create public policies in library service development across Indonesia. This study seeks to understand these laws through Natural Language Processing (NLP) and Latent Dirichlet allocation (LDA) Topic Modelling. Using these methods, we uncovered the major themes of these legal mandates for library services. Our research revealed five topics for each law. We then analyzed the NLI budgets from 2021 to 2023 to see how the key legal mandates were implemented. We found greater implementation of the 2007 Act than the 2018 Act. Our study offers new methods for library law and policy research.
Radial head replacement with the 3D-printed patient-specific titanium prosthesis: Preliminary results of a multi-centric prospective study
Authors: Luenam Suriya , Kosiyatrakul Arkaphat , Charoenlap Chris , Puncreobutr Chedtha , Lohwongwatana Boonrat
Published: March 2024

Purpose

To report preliminary clinical results and safety of 3D-printed patient-specific titanium radial head (RH) prosthesis in treatment of the irreparable RH fractures.

Material and methods

This multi-centric prospective study included 10 patients (6 men and four women, mean age 41 years (range, 25–64 years)). Three cases were classified as Mason type III and 7 cases as type IV. Patients were assessed preoperatively, intraoperatively, and at 1, 6, 12, 24, 36, and 48 weeks postoperatively. Range of motion (ROM), visual analog scale (VAS) score, Disabilities of the Arm, Shoulder and Hand (DASH) score, Mayo Elbow Performance Score (MEPS), radiology imaging, and laboratory blood and urine testing were evaluated.

Results

The prostheses were implanted utilizing cemented stems in 5 patients and cementless stems in 5 patients. Intraoperatively, well congruency of a prosthesis with capitellum and radial notch of ulna was observed in all cases. All patients had improvement of ROM, VAS score, DASH score, and MEPS during the postoperative follow-ups. At the final follow-up, mean elbow extension was 6.5° (range, 0°–30°), flexion 145° (range, 125°–150°), supination 79° (range, 70°–80°), and pronation 73.5° (range, 45°–80°). Mean VAS score was 0.3 (range, 0–3), DASH score was 12.35 (range, 1.7–23.3), and MEPS was 99.5 (range, 95–100). Postoperative radiographs demonstrated heterotopic ossification in 2 cases, periprosthetic radiolucency in 2 cases, and proximal radial neck resorption in 2 cases. No one had the evidence of capitellar erosion, implant failure, malpositioning, overstuffing, or symptomatic stem loosening. There was no significant alteration of laboratory results or adverse events related to the 3D-printed prosthesis implantation.

Conclusion

The preliminary results demonstrated that implantation of the 3D-printed patient-specific titanium RH prosthesis is safe and may be a potential treatment option for irreparable RH fracture.
Vaping in mental health inpatient units: A qualitative study of consumer and staff views on electronic nicotine delivery systems
Authors: Naylor Henry , Howie Alex , Every-Palmer Susanna
Published: March 2024

Objectives

The aim of this qualitative study was to explore the subjective experiences of consumers and staff members regarding the availability of electronic nicotine delivery systems (ENDS) in inpatient mental health units.

Methods

Mental health consumers and staff members ( n = 16) from rehabilitation and forensic inpatient units were interviewed in 2022. Thematic analysis of the transcripts was undertaken.

Results

Our study identified four themes: The high salience of nicotine use in inpatient units, delivering nicotine in a resource scarce environment, weighing up the harms of ENDS as a smoking cessation tool, and a need for fair and consistent policy.

Conclusions

The main positive aspects identified were recognition of rights of consumers, a relative harm reduction compared to tobacco use, and ENDS as a positive factor in the therapeutic relationship. The main challenges identified were resourcing issues, ENDS being a potential source of tension and conflict and a lack of overarching policy guiding their use.
Radar-Guided Localization and Resection for Metastatic Nodal and Soft Tissue Melanoma: A Single-Institution Retrospective Study
Authors: Beekman Kate E. , DePalo Danielle K. , Parker Lily M. , Elleson Kelly M. , Mullinax John E. , Sarnaik Amod A. , Sondak Vernon K. , Zager Jonathan S.
Published: March 2024

Background

Radar-guided localization (RGL) offers a wire-free, nonradioactive surgical guidance method consisting of a small percutaneously-placed radar reflector and handheld probe. This study investigates the feasibility, timing, and outcomes of RGL for melanoma metastasectomy.

Methods

We retrospectively identified patients at our cancer center who underwent RGL resection of metastatic melanoma between December 2020-June 2023. Data pertaining to patients’ melanoma history, management, reflector placement and retrieval, and follow-up was extracted from patient charts and analyzed using descriptive statistics.

Results

Twenty-three RGL cases were performed in patients with stage III-IV locoregional or oligometastatic disease, 10 of whom had reflectors placed prior to neoadjuvant therapy. Procedures included soft tissue nodule removals (8), index lymph node removals (13), and therapeutic lymph node dissections (2). Reflectors were located and retrieved intraoperatively in 96% of cases from a range of 2 to 282 days after placement; the last reflector was not able to be located during surgery via probe or intraoperative ultrasound. One retrieved reflector had migrated from the index lesion, thus overall success rate of reflector and associated index lesion removal was 21 of 23 (91%). All RGL-localized and retrieved index lesions that contained viable tumor (10) had microscopically negative margins. There were no complications attributable to reflector insertion and no unexpected complications of RGL surgery.

Conclusion

In our practice, RGL is a safe and effective surgical localization method for soft tissue and nodal melanoma metastases. The inert nature of the reflector enables implantation prior to neoadjuvant therapy with utility in index lymph node removal.
Do people with dementia and carers get what they need? Barriers in social care and carers needs assessments
Authors: Giebel Clarissa , Watson James , Dickinson Julie , Gabbay Mark , Halpin Kath , Harding Andrew , Swarbrick Caroline
Published: March 2024

Background

People with dementia and unpaid carers need to go through a social care or carers needs assessment to access and receive subsidised or fully-funded social care. With no previous evidence, this qualitative study aimed to provide insights into the access to, experiences of receiving and conducting social care or carers needs assessments, and access to social care.

Methods

Unpaid carers of people with dementia and professionals conducting social care or carers needs assessment living or working in England were interviewed remotely about their experiences between April and August 2023. Topic guides were co-produced with two unpaid carers, and both were supported to code anonymised transcripts. Thematic analysis was used to analyse the data.

Findings

Twenty-seven unpaid carers ( n = 21) and professionals ( n = 6) participated. Four themes were generated: (1) Issues with accessing needs assessments, not the process; (2) Knowledge of needs assessments and the health and social care system; (3) Expectations of unpaid carers; and (4) Post-assessment unmet needs. The most prominent barriers unpaid carers and their relatives with dementia encountered were awareness of and access to needs assessment. Unpaid carers were mostly unaware of the existence and entitlement to a needs assessment, and sometimes realised they had participated in one without their knowledge. Professionals described the pressures on their time and the lack of financial resources within services.

Conclusions

To facilitate improved access to dementia care and support for carers, the pathway to accessing needs assessments needs to be clearer, with better integration and communication between health and social care.
From impact to impacting: A pragmatist perspective on tackling grand challenges
Authors: Wegener Frithjof E , Lee Ju Young , Mascena Barbosa Alice , Sharma Garima , Bansal Pratima (Tima)
Published: March 2024

Scholars have long sought to impact management practice. However, the current conceptualization of impact is grounded in dualisms, separating researchers from managers, means from ends, and thought from action. Such a dualistic understanding of impact hampers researchers’ and managers’ ability to achieve impact. Nowhere is this issue more acute than in the context of grand challenges, which require researchers and managers to work together closely. As a way forward, we propose a pragmatist perspective on impact, where impact is not seen as a one-time, unidirectional event, but rather as a relational and recursive process. By overcoming dualisms in traditional approaches to impact, pragmatist impacting can help advance progress on grand challenges and our current understanding of co-creation. In this article, we illustrate pragmatist impact ing and reflect on its opportunities and challenges through our experience at Innovation North, an innovation laboratory that brought together researchers and managers to co-create a systems innovation process.
Pharmacomechanical thrombectomy with Angiojet in acute arterial occlusions: A prospective study among the results and outcomes
Authors: Soares Rafael de Athayde , Campos Ana Beatriz Campelo , Portela Matheus Veras Viana , Brienze Carolina Sabadoto , Brancher Giovana Quarentei Barros , Sacilotto Roberto
Published: March 2024

Objective

The main objective of this present paper was to evaluate the results and outcomes of patients with acute limb ischemia (ALI) submitted to pharmacomechanical thrombectomy (PMT) endovascular surgery with Angiojet, regarding the number of cycles/pumps.

Methods

Prospective, consecutive cohort study of ALI patients submitted to PMT endovascular intervention subdivided into two groups according to the number of cycles in the Angiojet technique: Group 1 higher than 150 cycles/second and Group 2 lesser than 150 cycles/second (cycles/s).

Results

Overall, 92 patients with ALI submitted to PMT were evaluated. Two groups of patients were identified: Group 1 higher than 150 cycles/s with 60 patients and Group 2 lesser than 150 cycles/s with 32 patients. The overall mortality rate (OMR) was 15.1% (13 patients) in total cohort within the first 30 days. Group 1 had a higher OMR than Group 2 (16.1% vs 9.3%, p = 0.007). There were 4 cases of hematuria (4.3%), all of them in Group 1. We have performed a Kaplan–Meier regarding limb salvage rates: Group 1 had 85% and Group 2 had 95.7% at 1057 days. P = 0.081. Among the factors evaluated, the following were related to overall mortality rate: PMT with higher >150 cycles/s (HR = 7.17, p = 0.007, CI: 1.38–8.89), COVID-19 infection (HR = 2.75, p = 0.010, CI = 1.73–5.97), and post-operative acute kidney injury (HR = 2.97, p < 0.001, CI = 1.32–8.13). Among the factors evaluated, the following was related to limb loss: post-operative acute kidney injury (HR = 4.41, p = 0.036, CI: 1.771–7.132), probably because patients experiencing limb loss have a higher incidence of acute renal insufficiency due to higher circulating myoglobin higher hemolysis from the increased Angiojet cycles inducing rhabdomyolysis.

Conclusion

PMT with Angiojet is a safe and effective therapy in patients with ALI. However, patients receiving greater than 150 cycles/s were noted to have higher rates of acute kidney injury and mortality. This is likely reflective of increased thrombus burden and higher rates of hemolysis. Acute kidney injury, greater than 150 cycles/s, and COVID-19 infection were the variables with the strongest association to perioperative mortality.
Post-reinforcement pauses during slot machine gambling are moderated by immersion
Authors: Murch W. Spencer , Ferrari Mario A , Clark Luke
Published: March 2024

The post-reinforcement pause (PRP) is an operant effect in which response latencies increase on trials following the receipt and consumption of reward. Human studies demonstrate analogous effects in electronic gambling machines that utilise random ratio reinforcement schedules. We sought to identify moderators of the human PRP effect, hypothesising that the magnitude of gamblers’ PRPs is moderated by the type of reinforcing outcome (genuine wins vs. losses-disguised-as-wins [LDWs] vs. free-spin bonus features) and individuals’ level of gambling immersion, a cognitive state linked to problem gambling. Experienced slot machine users ( N = 53) played a real slot machine for 20 min. The dependent variable was defined as the time delay in the initiation of each bet (“Spin Initiation Latency”; SIL). Using 80% of trials, a linear model was fit regressing SIL on the independent variables (outcome type, immersion, and outcome-by-immersion interaction), and a larger group of covariates (participant ID, trial number, winnings, etc.) selected using double-robust LASSO-regularised regression. The previously unseen 20% of cases were used to validate the model. Positively reinforcing outcome types (wins, LDWs, bonus spins) showed significantly larger SILs than losses, indicating a PRP effect. Immersion did not predict response latencies, but win-by-immersion and LDW-by-immersion interactions indicated that pauses were greater among more immersed participants. The small number of free-spin bonus features showed similar trends that were not statistically significant. These results indicate that gamblers immersed in play remained sensitive to in-game reinforcement (contrary to a prevailing account), and provide guidance for researchers bridging laboratory research and real-world behaviour.
Word association task responses prime associations in subsequent trials
Authors: Playfoot David , Burysek Ondrej
Published: March 2024

The word association task has been used extensively in psychological and linguistic research as a way of measuring connections between words in the mental lexicon. Interpretation of word association data has assumed that responses represent the strongest association between cue word and response, but there is evidence that participant behaviour can be affected by task instructions and design. This study investigated whether word association responses can be primed by the participants’ own response to the preceding cue—that is, whether the order in which cues are presented alters the responses that are generated. Results showed that the proportion of participants who provide a particular association (e.g., acid—RAIN) is greater when their response to the previous cue in the list is also associated with rain (e.g., parasol—UMBRELLA). The same is not true when the two cues are presented non-consecutively. Word association tasks should be administered such that the order in which cues are presented is random for every participant so as to avoid unintentional contamination of associative strength data.
Trajectories of physical well-being among adults with acute myeloid leukemia
Authors: Jensen-Battaglia Marielle , Sohn Michael B. , Consagra William , Wang Ying , Zhang Zhihong , LoCastro Marissa , Davis Jenae , Buettner Katheryn , Mortaz Soroush , El-Jawahri Areej R. , Loh Kah Poh
Published: March 2024

Patients with acute myeloid leukemia (AML) often undergo physical decline leading to negative outcomes. Identification of distinct trajectories may help guide clinical decision-making and supportive care interventions. We built group-based trajectory models (GBTM) to find trajectories of change in the Functional Assessment of Cancer Therapy Physical Well-Being (FACT-PWB) subscale (up to 5 time points over 0 to 200 days of follow-up) using data from adults with newly diagnosed AML in 4 supportive care studies. We also estimated the association of baseline characteristics (age, marital status, education, AML risk, baseline FACT-PWB, depression, and anxiety) with group membership. Among 343 patients with ≥2 FACT-PWB scores, mean age was 69.6 years (standard deviation, 12.1); most had intermediate-risk AML (n = 178 [51.8%]), received intensive treatment (n = 244 [71.1%]), and died during follow-up (n = 199 [58.0%]). The GBTM with 4 distinct trajectories showed the best fit. The largest group (n = 153 [45.0%]) showed slight improvement, whereas the smallest (n = 8 [2.4%]) experienced early decline with later improvement. Baseline FACT-PWB was the only characteristic statistically significantly associated with group membership. Adults with AML show distinct trajectories of physical well-being, and many experience some decline. Exploring trajectories of self-reported and objective physical function may inform decision-making and interventions. These trials were registered at www.ClinicalTrials.gov as #NCT02975869, #NCT03310918, and #NCT03372291.
Salvage therapies including retreatment with BCMA-directed approaches after BCMA CAR-T relapses for multiple myeloma
Authors: Reyes Kevin R. , Liu Yen-Chun , Huang Chiung-Yu , Banerjee Rahul , Martin Thomas , Wong Sandy W. , Wolf Jeffrey L. , Arora Shagun , Shah Nina , Chari Ajai , Chung Alfred
Published: March 2024

For patients with relapsed/refractory multiple myeloma with a relapse after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell therapy (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAbs) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. With a median follow-up of 13.5 months, median overall survival from time of relapse until death was 18 months (95% confidence interval [CI], 13.2 to not reached [NR]). Fifty-eight patients received subsequent myeloma-directed therapies, with a total of 265 lines of therapy (LOTs). The overall response rate for firstline salvage therapy was 41% (95% CI, 28-55). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAbs (60%), CD38-directed combinations (80% when combined with BsAb; 50% when combined with immunomodulatory drugs and/or proteasome inhibitors), and alkylator-combinations (50% overall; 69% with high-dose alkylators). Thirty-four patients received at least 1 line of salvage BCMA-directed therapy; median progression-free survival was 8.3 months (95% CI, 7.9 to NR), 3.6 months (95% CI, 1.4 to NR), and 1 month (95% CI, 0.9 to NR) with median duration of response (DOR) of 8 months, 4.4 months, and 2.8 months for subsequent BCMA-directed CAR-T, BsAb, and belantamab mafadotin, respectively. Retreatment with BCMA-directed CAR-T and BsAbs can be effective salvage options after BCMA-directed CAR-T relapse; however, DORs appear limited, and further studies with new combinations and alternative targets are warranted.
Haploidentical stem cell donor choice for patients with acute myeloid leukemia: a study from the ALWP of the EBMT
Authors: Sanz Jaime , Labopin Myriam , Blaise Didier , Raiola Anna Maria , Busca Alessandro , Vydra Jan , Tischer Johanna , Chevallier Patrice , Bramanti Stefania , Fanin Renato , Socié Gérard , Forcade Edouard , Kröger Nicolaus , Koc Yener , Itäla-Remes Maija , Zecca Marco , Nagler Arnon , Brissot Eolia , Spyridonidis Alexandros , Bazarbachi Ali , Giebel Sebastian , Piemontese Simona , Mohty Mohamad , Ciceri Fabio
Published: March 2024

There is a paucity of information to guide the selection of the most suitable donor in haploidentical (Haplo) hematopoietic stem cell transplantation (HSCT). For this reason, from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we conducted a retrospective analysis to evaluate the impact of Haplo donor characteristics on outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease prophylaxis with posttransplant cyclophosphamide (PTCy). The primary end point was graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS). Overall, 2200 patients were included. The median age of donors was 37 years (range, 8-71); 820 (37%) were females, including 458 (21%) who were used for male recipients. In addition, 1631 donors (74%) donated peripheral blood (PB). Multivariable analysis identified certain donor-related risk factors with a detrimental impact on transplant outcomes. The use of PB, older donors’ ages (>37 years), and female donors to male recipients negatively affected GRFS. Donor’s age and female donor-to-male recipient combination also affected nonrelapse mortality, leukemia-free survival, and overall survival. In conclusion, donor-related variables significantly influence outcomes in patients with AML after Haplo-HSCT with PTCy. When possible, younger donors and male donors for male recipients should be prioritized. The use of bone marrow can additionally prevent GVHD.
Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab
Authors: Chandrakasan Shanmuganathan , Jordan Michael B. , Baker Ashley , Behrens Edward M. , Bhatla Deepika , Chien May , Eckstein Olive S. , Henry Michael M. , Hermiston Michelle L. , Hinson Ashley P. , Leiding Jennifer W. , Oladapo Abiola , Patel Sachit A. , Pednekar Priti , Ray Anish K. , Dávila Saldaña Blachy , Sarangi Susmita N. , Walkovich Kelly J. , Yee John D. , Zoref-Lorenz Adi , Allen Carl E.
Published: March 2024

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, or progressive disease, or intolerance with conventional HLH treatments. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. In total, 46 patients met the pHLH classification criteria. Median age at diagnosis was 1.0 year (range, 0.3-21.0). Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15 of 46 patients were in the intensive care unit, and 35 of 46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (24/33, 72.7%), ferritin (20/45, 44.4%), fibrinogen (37/38, 97.4%), platelets (39/46, 84.8%), and absolute neutrophil count (40/45, 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pretransplant survival was 38 of 42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant, and 23 of 31 (74.2%) of those who received transplant were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.
It is feasible and safe to stop specialized follow-up of asymptomatic lower-risk chronic lymphocytic leukemia
Authors: Brieghel Christian , da Cunha-Bang Caspar , Mourek Jindrich , Kjeldsen Lars , Niemann Carsten U.
Published: March 2024

Approximately half of patients with chronic lymphocytic leukemia (CLL) will never require treatment; nonetheless, they are recommended life-long specialized follow-up (sFU). To prioritize health care resources, local hospital management implemented ending sFU in asymptomatic patients with CLL International Prognostic Index (CLL-IPI) and CLL without need of treatment (CLL-WONT) low-to-intermediate risk, who were covered by universal health care. To evaluate the feasibility and safety of ending sFU, we investigated 3-year clinical outcomes among 112 patients selected by clinical assessment to end sFU as compared with 88 patients selected to continue sFU. Patients who ended sFU were older, but otherwise lower risk compared with patients continuing sFU. Overall survival (OS) was similar in patients ending and continuing sFU (3-year OS, 87% and 80%, respectively; P = .16). Hospital visits per patient-year were lower (median 0.7 vs 4.3, P < .0001) and time to first infection was longer (P = .035) in patients ending sFU compared with those who continued sFU, including shorter in-hospital antimicrobial treatment (median 4 vs 12 days, respectively; P = .026). Finally, 1 in 6 patients were rereferred, including 4 patients meeting international workshop on CLL criteria for need of treatment. This also resulted in a lower 3-year first treatment rate for patients ending sFU compared with patients continuing sFU (4% vs 23%, respectively; P < .0001). In conclusion, it is feasible and safe to end sFU for patients with CLL who have low-to-intermediate risk CLL-IPI and CLL-WONT scores upon thorough clinical evaluation before ending sFU.
Racial/ethnic disparities in availability of volunteer unrelated donors for allogeneic transplantation
Authors: Fingrut Warren B. , Davis Eric , Archer Anne , Brown Samantha , Devlin Sean , Nhaissi Melissa , Rapoport Candice , Chinapen Stephanie , Kelly Amanda , Wells Deborah , Scaradavou Andromachi , Gyurkocza Boglarka , Papadopoulos Esperanza , Politikos Ioannis , Shaffer Brian C. , Barker Juliet N.
Published: March 2024

Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness scores. Of URDs requested for confirmatory HLA-typing (CT) alone (ie, without simultaneous workup), 1,894 of 3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness score was highly predictive of CT availability. More non-European patients (n = 120) than Europeans (n = 335) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889 [68%]) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients being 150/458 (33%), 120/258 (47%), and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness scores, centers should pursue, and registries permit, simultaneous pursuit of many URDs and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, although registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplant for all.
Unexpected early loosening of rectangular straight femoral Zweymüller stems with an alumina-reduced surface after total hip arthroplasty—a prospective, double-blind, randomized controlled trial
Authors: Moret Céline S. , Masri Salim El , Schelker Benjamin L. , Friederich Niklaus F. , Hirschmann Michael T.
Published: March 2024

Background

Alumina particles from the grit blasting of Ti-alloy stems are suspected to contribute to aseptic loosening. An alumina-reduced stem surface was hypothesized to improve osseointegration and show comparable short-term outcomes to those of a standard stem.

Methods

In this prospective, double-blind, randomized trial, 26 standard (STD) and 27 experimental new technology (NT) stems were implanted. The latter were additionally treated by acid etching and ice blasting to remove alumina particles from the grit-blasting process. Follow-up occurred at 12 and 24 months. Bone mineral density (BMD) around the stem was measured by a dual-energy x-ray absorptiometry device (DEXA). Radiographs were reviewed for alterations. Clinical scoring comprised the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Harris Hip Score (HHS). Survival rates were calculated up to 50 months.

Results

Lower mean BMD and more severe cortical hypertrophies were found in the NT group. At 12 months, radiolucent lines were observed mostly in the metaphyseal zone for both groups, with a progression tendency in the NT group at 24 months. At 12 months, pain scores and the WOMAC total and physical activity scores were significantly lower in the NT group, without any differences thereafter. The number of NT stem revisions amounted to 6 (24%) and 11 (41%) at 24 and 50 months, respectively.

Conclusion

In the NT group, unexpected catastrophic failure rates of 41% caused by early aseptic loosening were noted within 50 months. Compared with the STD stems, NT stems lead to poor clinical and radiographic results.

Level of evidence: II.

Trial Registration: NCT05053048.
Nrf2 activation: a key mechanism in stem cell exosomes-mediated therapies
Authors: Vahidinia Zeinab , Azami Tameh Abolfazl , Barati Shirin , Izadpanah Melika , Seyed Hosseini Elahe
Published: March 2024

Exosomes are nano-sized membrane extracellular vesicles which can be released from various types of cells. Exosomes originating from inflammatory or injured cells can have detrimental effects on recipient cells, while exosomes derived from stem cells not only facilitate the repair and regeneration of damaged tissues but also inhibit inflammation and provide protective effects against various diseases, suggesting they may serve as an alternative strategy of stem cells transplantation. Exosomes have a fundamental role in communication between cells, through the transfer of proteins, bioactive lipids and nucleic acids (like miRNAs and mRNAs) between cells. This transfer significantly impacts both the physiological and pathological functions of recipient cells. Nuclear factor erythroid 2–related factor 2 (Nrf2), a transcription factor, is able to mitigate damage caused by oxidative stress and inflammation through various signaling pathways. The positive effects resulting from the activation of the Nrf2 signaling pathway in different disorders have been documented in various types of literature. Studies have confirmed that exosomes derived from stem cells could act as Nrf2 effective agonists. However, limited studies have explored the Nrf2 role in the therapeutic effects of stem cell-derived exosomes. This review provides a comprehensive overview of the existing knowledge concerning the role of Nrf2 signaling pathways in the impact exerted by stem cell exosomes in some common diseases.

Graphical Abstract
Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention
Authors: Lämmerhirt Lisa , Kappelmann-Fenzl Melanie , Fischer Stefan , Meier Paula , Staebler Sebastian , Kuphal Silke , Bosserhoff Anja-Katrin
Published: March 2024

Malignant melanoma remains the most lethal form of skin cancer, exhibiting poor prognosis after forming distant metastasis. Owing to their potential tumor-suppressive properties by regulating oncogenes and tumor suppressor genes, microRNAs are important player in melanoma development and progression. We defined the loss of miR-101-3p expression in melanoma cells compared with melanocytes and melanoblast-related cells as an early event in tumor development and aimed to understand the tumor suppressive role of miR-101-3p and its regulation of important cellular processes. Reexpression of miR-101-3p resulted in inhibition of proliferation, increase in DNA damage, and induction of apoptosis. We further determined the nuclear structure protein Lamin B1, which influences nuclear processes and heterochromatin structure, ATRX, CASP3, and PARP as an important direct target of miR-101-3p. RNA sequencing and differential gene expression analysis after miR-101-3p reexpression supported our findings and the importance of loss of mir-101-3p for melanoma progression. The validated functional effects are related to genomic instability, as recent studies suggest miRNAs plays a key role in mediating this cellular process. Therefore, we concluded that miR-101-3p reexpression increases the genomic instability, leading to irreversible DNA damage, which leads to apoptosis induction. Our findings suggest that the loss of miR-101-3p in melanoma serves as an early event in melanoma progression by influencing the genomic integrity to maintain the increased bioenergetic demand.
Biofortified Rice Provides Rich Sakuranetin in Endosperm
Authors: Zhao Yao , Hu Jitao , Zhou Zhongjing , Li Linying , Zhang Xueying , He Yuqing , Zhang Chi , Wang Junmin , Hong Gaojie
Published: March 2024

Sakuranetin plays a key role as a phytoalexin in plant resistance to biotic and abiotic stresses, and possesses diverse health-promoting benefits. However, mature rice seeds do not contain detectable levels of sakuranetin. In the present study, a transgenic rice plant was developed in which the promoter of an endosperm-specific glutelin gene OsGluD-1 drives the expression of a specific enzyme naringenin 7-O-methyltransferase (NOMT) for sakuranetin biosynthesis. The presence of naringenin, which serves as the biosynthetic precursor of sakuranetin made this modification feasible in theory. Liquid chromatography tandem mass spectrometry (LC–MS/MS) validated that the seeds of transgenic rice accumulated remarkable sakuranetin at the mature stage, and higher at the filling stage. In addition, the panicle blast resistance of transgenic rice was significantly higher than that of the wild type. Specially, the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging was performed to detect the content and spatial distribution of sakuranetin and other nutritional metabolites in transgenic rice seeds. Notably, this genetic modification also did not change the nutritional and quality indicators such as soluble sugars, total amino acids, total flavonoids, amylose, total protein, and free amino acid content in rice. Meanwhile, the phenotypes of the transgenic plant during the whole growth and developmental periods and agricultural traits such as grain width, grain length, and 1000-grain weight exhibited no significant differences from the wild type. Collectively, the study provides a conceptual advance on cultivating sakuranetin-rich biofortified rice by metabolic engineering. This new breeding idea may not only enhance the disease resistance of cereal crop seeds but also improve the nutritional value of grains for human health benefits.
Circadian rhythm of intraocular pressure
Authors: Ikegami Keisuke
Published: March 2024

Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na+/K+-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the β1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.
Genome-wide identification and expression profiling of the ABI5 gene family in foxtail millet (Setaria italica)
Authors: Wen Yinyuan , Zhao Zeya , Cheng Liuna , Zhou Shixue , An Mengyao , Zhao Juan , Dong Shuqi , Yuan Xiangyang , Yin Meiqiang
Published: March 2024

Background

ABA Insensitive 5 (ABI5) is a basic leucine zipper transcription factor that crucially influences plant growth, development, and stress response. However, there is minimal research on the ABI5 family in foxtail millet.

Results

In this study, 16 ABI5 genes were identified in foxtail millet, and their sequence composition, gene structures, cis-acting elements, chromosome positions, and gene replication events were analyzed. To more thoroughly evaluate the developmental mechanisms of the SiABI5 family during evolution, we selected three dicotyledons (S. lycopersicum, A. thaliana, F. tataricum) and three (Z. mays, O. sativa, S. bicolor) specific representative monocotyledons associated with foxtail millet for comparative homology mapping. The results showed that foxtail millet ABI5 genes had the best homology with maize. A promoter sequence analysis showed that the SiABI5s contain numerous cis-acting elements related to hormone and stress responses, indicating that the regulation of SiABI5 expression was complex. The expression responses of 16 genes in different tissues, seed germination, and ear development were analyzed. A total of six representative genes were targeted from five subfamilies to characterize their gene expression responses to four different abiotic stresses. Overexpression of SiABI5.12 confers tolerance to osmotic stress in transgenic Arabidopsis thaliana, which demonstrated the function of SiABI5 responded to abiotic stress.

Conclusions

In summary, our research results comprehensively characterized the SiABI5 family and can provide a valuable reference for demonstrating the role of SiABI5s in regulating abiotic stress responses in foxtail millet.
Auxin and carbohydrate control flower bud development in Anthurium andraeanum during early stage of sexual reproduction
Authors: Wan Xiao , Zou Long-Hai , Pan Xiaoyun , Ge Yaying , Jin Liang , Cao Qunyang , Shi Jiewei , Tian Danqing
Published: March 2024

Background

Flower buds of Anthurium andraeanum frequently cease to grow and abort during the early flowering stage, resulting in prolonged planting times and increased commercialization costs. Nevertheless, limited knowledge exists of the mechanism of flower development after initiation in A. andraeanum.

Results

In this study, the measurement of carbohydrate flow and intensity between leaves and flowers during different growth stages showed that tender leaves are strong sinks and their concomitant flowers are weak ones. This suggested that the tender leaves compete with their concomitant flower buds for carbohydrates during the early growth stages, potentially causing the abortion of the flower buds. The analysis of transcriptomic differentially expressed genes suggested that genes related to sucrose metabolism and auxin response play an important role during flower bud development. Particularly, co-expression network analysis found that AaSPL12 is a hub gene engaged in flower development by collaborating carbohydrate and auxin signals. Yeast Two Hybrid assays revealed that AaSPL12 can interact with AaARP, a protein that serves as an indicator of dormancy. Additionally, the application of exogenous IAA and sucrose can suppress the expression of AaARP, augment the transcriptional abundance of AaSPL12, and consequently expedite flower development in Anthurium andraeanum.

Conclusions

Collectively, our findings indicated that the combination of auxin and sugar signals could potentially suppress the repression of AaARP protein to AaSPL12, thus advancing the development of flower buds in Anthurium andraeanum.
Is Takotsubo syndrome induced by patent ductus arteriosus occlusion?
Authors: Li Shuhao , Yang Senyan , Zhou Shujing , Zhang Shuang , Li Xueying , Zhang Haibo , Ren Ping , Liu Yanwu , Liu Ying , Chen Yuanguo
Published: March 2024

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.
Can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients?
Authors: Zareei Mohammad , Zareiamand Hossein , Kamali Mahsa , Ardalani Nasim , Ebrahimi Ata , Nabati Maryam
Published: March 2024

Background

The present study aimed to respond to clinical question, can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients?

Methods

This descriptive-analytical study was conducted on cardiac patients. All of the non-ST elevation acute coronary syndrome (NSTEACS) including non-ST elevation myocardial infarction (NSTEMI) and unstable angina patients included in the study. Then they divided into two groups: prolonged P-R interval and normal P-R interval. The patients who had a history of digoxin and calcium channel blocker use, using antiarrhythmic drugs, known valvular or congenital heart disease and connective tissue, unreadable P-R interval and cardiac block were excluded. Data were collected using the questionnaire consisted demographic data and clinical outcomes and a follow-up part was completed by one of the researchers.

Results

Finally, 248 patients completed the study. The results showed both of the two groups had significant differences in terms of the history of myocardial infarction (MI) (p = 0.018), the level of high-density lipoprotein (HDL) (p = 0.004), heart rate (p = 0.042), inverted T wave (p = 0.017), anterior ST- segment depression (p = 0.008), normal report of coronary angiography (CAG) (p = 0.003), three vessels disease (p = 0.043), left main lesion (p = 0.045) and SYNTAX score (p = 0.032) based on the CAG report. The results of six-month follow-up showed although, the frequency of ischemic stroke, coronary artery disease (CAD) and cardiovascular death were higher in prolonged P-R interval groups. The chi-square test showed this difference was statistically non-significant (p > 0.05). The multivariate logistic regression model revealed non-significant relationships between prolonged P-R interval and SYNTAX score, significant CAD, three-vessel disease, inverted T wave, anterior ST depression, heart rate and HDL.

Conclusions

Based on the results of our study the six-month follow-up showed non-significant outcomes. Further studies are recommended to assess the long-term outcomes.