bluuebunny/crossref_metadata_2025 huggingface dataset:
AXLerate-OC/GOG-3059/ENGOT OV-66: Results of a phase 3, randomized, double-blind, placebo/paclitaxel-controlled study of batiraxcept (AVB-S6-500) in combination with paclitaxel in patients with platinum-resistant recurrent ovarian cancer.
Authors: Fuh Katherine Cynthia , Tsitsishvili Zaza , Reid Thomas J. , De Giorgi Ugo , Hand Lauren , Bowen Rebecca , Miller Devin , Vulsteke Christof , Sharma Sudarshan K. , Chudecka-Głaz Anita M. , Liu Joyce F. , Eberst Lauriane , Neff Robert , Lim Peter C , Iglesias David A. , Jenkins Vogel Tilley , Myers Tashanna K. N. , González-Martín Antonio , Gonzalez Martin Antonio
Published: June 2024

LBA5515

Background: Batiraxcept is an Fc-fusion protein engineered to have a 200-fold higher affinity than wild-type AXL for its activating ligand GAS6. Batiraxcept sequesters GAS6 and inhibits its interaction with AXL. The Phase 1b study demonstrated safety with batiraxcept in combination with paclitaxel. Methods: This was a global, placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT04729608). Patients with PROC were randomly assigned 1:1 to receive intravenous batiraxcept every 2 weeks (D1, 15 every 28 days) with once-a-week IV paclitaxel (D1, 8, 15 every 28 days) or placebo with paclitaxel until disease progression. The primary endpoint was progression-free survival as assessed by investigator-assessed progression-free survival and secondary endpoint was overall survival. The randomization was stratified by platinum-free interval (< 3 months, 3 to 6 months), prior lines (1 to 2, 3 to 4), and prior bevacizumab status (yes, no). Exploratory endpoints include objective response rate, duration of response, quality of life, clinical benefit rate, and pharmacokinetic and pharmacodynamic profile. Results: A total of 366 participants were randomly assigned, and analysis was performed based on intent-to-treat. There were 183 participants who had prior bevacizumab and 177 with no prior bevacizumab. Median PFS (mPFS) was 5.13 months in the batiraxcept + paclitaxel arm and 5.49 months in the control paclitaxel arm, hazard ratio (HR) 1.29 (CI, 1.01 to 1.64; p=0.98). Median OS with batiraxcept + paclitaxel was 14.29 months versus 14.39 months, HR 1.06 (CI 0.77 to 1.46; p=0.64). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 25.1% with batiraxcept + paclitaxel versus 26.2% with control paclitaxel arm. An exploratory analysis of the 304 evaluable tumors found that 61 (20%) of tumors had high AXL expression by immunohistochemistry (IHC). In participants with high tumor AXL expression, median PFS was 5.78 months in the batiraxcept + paclitaxel arm and 3.71 months in the control paclitaxel arm, HR 0.55 (CI, 0.31 to 0.98; p=0.042). For high AXL expressing tumors, median OS was 17.8 months in the batiraxcept + paclitaxel cohort and 8.11 months in the paclitaxel cohort, HR 0.32 (CI, 0.14 to 0.73; p=0.006). Conclusions: The addition of batiraxcept to paclitaxel did not improve PFS or OS. However, in AXL high tumors, the PFS and OS were higher in participants who received batiraxcept with paclitaxel compared to paclitaxel alone. Clinical trial information: NCT04729608 .
Long term results of a randomized phase III study of nimotuzumab in combination with concurrent radiotherapy and cisplatin versus radiotherapy and cisplatin alone, in locally advanced squamous cell carcinoma of the head and neck.
Authors: Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Shah Minit Jalan , Ghosh Sarbani Laskar , Budrukkar Ashwini , Swain Monali , Balaji Arun , Chaukar Devendra , Pai Prathamesh S , Chaturvedi Pankaj , Prabhash Kumar
Published: June 2024

LBA6092

Background: The addition of nimotuzumab to weekly cisplatin as a radiosensitizer had improved progression-free survival (PFS) in a phase 3 study in locally advanced head and neck squamous cell carcinoma (LA HNSCC). However, whether it leads to an improvement in long-term OS is unknown. Hence this analysis was performed to evaluate the efficacy (in terms of OS) and late-term adverse events of the addition of nimotuzumab to concurrent chemoradiation in LA HNSCC. Methods: This was an open-label, investigator-initiated, phase 3 randomized trial conducted from 2012 - 2018. 536 adult patients with LA HNSCC, fit for radical chemoradiation were randomly assigned. Primary sites in the nasopharynx, salivary gland, nasal cavity, and paranasal sinus were excluded. Randomized 1:1 to either radical radiotherapy (66-70 Gy) with concurrent weekly cisplatin (30 mg/m2) (CRT) or the same schedule of chemoradiation with weekly nimotuzumab (200 mg) (NCRT). The primary endpoint was a 10-year OS; the key secondary endpoint was late adverse events. Intent to treat analysis was performed. OS was defined as the time from randomization till death. Kaplan Meier method will be used for the estimation of OS. Landmark analysis was performed to compare 10 OS between the 2 arms. COX proportional hazard model will be used for the calculation of hazard ratio (HR). The adverse events between the 2 arms were compared using a Fisher's test. A p-value of 0.05 will be considered as significant. Results: The median follow-up was 8.86 years (95% CI 8.59-9.16). The primary site of the primary was the oropharynx (269,50.2%) and only 24 cases were HPV positive. The 10-year OS was 22.5% (95% CI 16.7-28.8) versus 33.5% (95% CI 27.6-39.4) in the CRT and NCRT arm respectively (Hazard ratio=0.811; 95%CI 0.664-0.995, P=0.044). The median OS was 2.78 years (95% CI 2.31-3.69) versus 3.69 years (95% CI 2.90-4.49) in the CRT and NCRT arm respectively (P value by log-rank test=0.04). The median OS in HPV negative oropharynx was 1.8 years (95% CI 1.51-2.09) versus 2.48 years (95% CI 1.79-3.16) in the CRT and NCRT arm respectively (P value by log-rank test=0.02; HR 0.724 95%CI 0.546-0.959). Long-term adverse events were captured in 380 patients. There was no statistically significant difference in late-term adverse events between the 2 arms and will be presented at the conference. Conclusions: The addition of nimotuzumab to weekly cisplatin leads to improvement in long-term overall survival in locally advanced HNSCC without any additional increase in late-term adverse events. These results are largely applicable in HPV-negative patients. Clinical trial information: CTRI/2014/09/004980 .
Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study.
Authors: Solomon Benjamin J. , Liu Geoffrey , Felip Enriqueta , Mok Tony S. K. , Soo Ross Andrew , Mazieres Julien , Shaw Alice Tsang , de Marinis Filippo , Goto Yasushi , Wu Yi-Long , Kim Dong-Wan , Martini Jean-Francois , Messina Rossella , Paolini Jolanda , Polli Anna , Thomaidou Despina , Toffalorio Francesca , Bauer Todd Michael
Published: June 2024

LBA8503

Background: Lorlatinib, a brain-penetrant, 3rd-generation ALK tyrosine kinase inhibitor, demonstrated improved progression-free survival (PFS) and intracranial (IC) activity vs crizotinib in the phase 3 CROWN study in treatment-naïve patients (pts) with advanced ALK+ non-small cell lung cancer (NSCLC). We report long-term efficacy and safety outcomes from the CROWN study after 5 years of follow-up. Methods: 296 treatment-naïve pts with advanced ALK+ NSCLC were randomized 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). In this post hoc analysis, we present investigator-assessed efficacy outcomes, safety, and biomarker analyses. Formal statistical testing was not performed. Results: As of October 31, 2023, 74 of 149 pts (50%) vs 7 of 142 pts (5%) were still receiving lorlatinib vs crizotinib. With a median duration of follow-up for PFS (95% CI) of 60.2 months (57.4-61.6) in the lorlatinib and 55.1 months (36.8-62.5) in the crizotinib arm, median PFS (95% CI) was not reached (NR; 64.3-NR) with lorlatinib and 9.1 months (7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.27). 5-year PFS (95% CI) was 60% (51-68) with lorlatinib and 8% (3-14) with crizotinib. Median time to IC progression (95% CI) was NR (NR-NR) with lorlatinib and 16.4 months (12.7-21.9) with crizotinib (HR, 0.06; 95% CI, 0.03-0.12). In pts without baseline brain metastases in the lorlatinib arm, only 4 of 114 developed brain progression, occurring within the first 16 months of treatment. Efficacy outcomes by baseline brain metastases are shown in the Table. Grade 3/4 adverse events (AEs) occurred in 77% of pts with lorlatinib and in 57% of pts with crizotinib. Treatment-related AEs led to treatment discontinuation in 5% and 6% of pts in the lorlatinib and crizotinib arms, respectively. Safety profile was consistent with that observed in prior analyses. Emerging new ALK mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment (n = 31). Conclusions: After 5 years of follow up, the median PFS in the lorlatinib arm has yet to be reached, corresponding to the longest PFS ever reported in advanced NSCLC. Coupled with prolonged IC efficacy and absence of new safety signals, these results indicate an unprecedented improvement in outcomes for pts with advanced ALK+ NSCLC. Clinical trial information: NCT03052608 . [Table: see text]
Ipilimumab and nivolumab plus UV1, an anticancer vaccination against telomerase, in advanced melanoma.
Authors: Lorigan Paul , Medina Theresa , Nyakas Marta , Rutten Annemie , Feun Lynn G. , Cowey Charles Lance , Payne Miranda , Hussain Israr , Kuzel Timothy , O'Day Steven , Sheri Amna , Friedlander Philip Adam , Kumar Satish , Bjorheim Jens , Bechter Oliver Edgar
Published: June 2024

LBA9519

Background: The combination of ipilimumab (IPI) and nivolumab (NIVO) remains a standard of care for patients with advanced melanoma, especially those with poor prognostic factors, albeit with a significant risk of toxicity. Therapeutic cancer vaccines are ideally positioned to improve outcomes without significantly increasing toxicity. UV1 is a therapeutic cancer vaccine generating T-cell responses against the universal cancer antigen telomerase. In a Phase I trial in melanoma (N = 30), UV1 plus pembrolizumab demonstrated a tolerable safety profile, a complete response rate of 33%, median PFS of 18.9 months, and 2-year OS rate of 73.3%. Recently, results from a randomized Phase II trial indicated a longer overall survival and a higher response rate for previously treated patients with advanced mesothelioma receiving UV1 in combination with IPI-NIVO (1). Methods: In this Phase II, open-label, multicenter study, we randomly assigned treatment-naïve patients with unresectable or metastatic melanoma (stage IIIb-IIId or IV) to IPI 3mg/kg + NIVO 1mg/kg for 4 cycles, followed by NIVO 480 mg as maintenance, with or without 8 intradermal injections of 300 µg UV1 (+GM-CSF). The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) according to RECIST 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response, and safety. Results: A total of 156 patients underwent randomization; 78 patients were assigned to the IPI-NIVO-UV1 arm and 78 patients to the IPI-NIVO arm. The median age was 60, 48% had M1C or D disease, 38% had LDH >upper limit of normal, and 42% had a positive BRAF mutation status. With a minimum follow-up of 18 months, the 12-month PFS rate was 57% in both arms (HR 0.95, 95% CI 0.59-1.55, p value 0.845). The ORR was similar with IPI-NIVO-UV1 compared to IPI-NIVO, at 60% vs 59%, respectively (Odds ratio 1.12, 95% CI 0.58-2.16, p value 0.867). The 12-month OS rate was 87% and 88%, respectively (HR 1.15, 95% CI 0.60-2.20, p value 0.674). The occurrence of grade >3 adverse events was similar in both treatment arms. Conclusion: UV1 did not improve on outcomes of IPI-NIVO, in terms of PFS. Longer follow-up is required for the accurate assessment of OS. No significant toxicity increases were observed with the addition of UV1. Data from a biomarker driven cohort are awaited. 1. Helland et al, Eur J Cancer 2024. Clinical trial information: NCT04382664 .
Quality of life with neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) versus adjuvant nivolumab in resectable stage III melanoma: 36-week data from the phase 3 NADINA trial.
Authors: Lucas Minke W. , Arokoski Reetta , Menzies Alexander M. , Pulleman Saskia , Saw Robyn P.M. , van Houdt Winan J. , Faries Mark B , Robert Caroline , Ascierto Paolo Antonio , Lebbe Celeste , Carlino Matteo S. , Kapiteijn Ellen , Suijkerbuijk Karijn , Rutkowski Piotr , Sandhu Shahneen , Van Der Veldt Astrid Aplonia Maria , Long Georgina V. , Blank Christian U. , van de Poll-Franse Lonneke , Lijnsvelt Judith
Published: June 2024

LBA9584

Background: Neoadjuvant (neoadj) ipilimumab (IPI) + nivolumab (NIVO) showed improved event-free survival compared to adjuvant (adj) NIVO, but at the cost of increased immune related toxicity (irAEs). In the PRADO trial, impairment of health-related quality of life (HRQoL) was predominantly driven by the extent of the surgery and not by irAEs. To evaluate the effect of neoadj IPI+NIVO on HRQoL, we report the 36w HRQoL outcomes from the phase 3 NADINA trial. Methods: Eligible patients (pts) with resectable, macroscopic stage III melanoma were randomly assigned to receive 2 cycles of neoadj IPI+NIVO followed by a therapeutic lymph node dissection (TLND; w6) and only in partial- or non-responders, 1y of adj systemic treatment; or TLND (w0) followed by 12 cycles adj NIVO. EORTC QLQ-C30 questionnaires (qtn) were digitally collected at baseline, w6, w12 and thereafter q12w. The unadjusted HRQoL scores (scale 0-100) were assessed for pts who completed 39w of follow-up (FU) on January 12, 2024. Results: 261/423 randomized pts had 39w FU at data cutoff. 81% completed the qtn at BL, with thereafter an average compliance of 80%. QLQ-C30 data were available for 107 pts in the neoadj arm and 103 in the adj arm. Physical-, role-, emotional functioning, and pain were comparable between the neoadj and adj arm across all timepoints (Table), as were fatigue and the summary score. A numerical trend towards worsening of physical-, role functioning, and pain was seen at w6 for the adj arm and at w12 for the neoadj arm, representing the post-surgery QoL timepoints. Conclusion: Using fully digitalized data collection, this first HRQoL analysis of neoadj vs adj immunotherapy in stage III melanoma showed comparable results between the neoadj and adj arms. Physical-, role functioning, and pain were impaired in both groups at the first post-surgery timepoint. Clinical trial information: NCT04949113 . [Table: see text]
Impact of a Multidisciplinary Supportive Care Model Using Distress Screening at an Asian Ambulatory Cancer Center: A Cluster Randomized Controlled Trial
Authors: Ke Yu , Neo Patricia Soek Hui , Yang Grace Meijuan , Neo Shirlyn Hui-Shan , Tan Yung Ying , Tan Yee Pin , Ramalingam Mothi Babu , Loh Kiley Wei-Jen , Quah Daniel Song Chiek , Chew Lita , Si Phebe En Hui , Chan Raymond Javan , Hwang William Ying Khee , Chan Alexandre
Published: June 2024

PURPOSE

The Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) program adopts a multidisciplinary supportive care model with routine distress screening to triage newly diagnosed cancer survivors for additional support on the basis of distress levels. This study aimed to evaluate the clinical impact of ACCESS over 1 year.

METHODS

We performed cluster random assignment at the oncologist level in a 1:1 ratio to receive ACCESS or usual care. Participants 21 years and older, newly diagnosed with breast or gynecologic cancer, and receiving care at National Cancer Centre Singapore were included. Outcomes assessed every 3 months for 1 year included quality of life (QoL) (primary), functioning, physical and psychological symptom burden, and activity levels. Data were analyzed using mixed-effects models.

RESULTS

Participants from 16 clusters (control = 90, intervention = 83) were analyzed. The ACCESS program did not significantly improve QoL (primary outcome). However, compared with usual care recipients, ACCESS recipients reported higher physical functioning ( P = .017), role functioning ( P = .001), and activity levels ( P < .001) at 9 months and lower psychological distress ( P = .025) at 12 months. ACCESS recipients screened with high distress had poorer QoL, lower role and social functioning, and higher physical symptom distress at 3 months but had comparable scores with ACCESS recipients without high distress after 12 months.

CONCLUSION

Compared with usual care, participation in the ACCESS program did not yield QoL improvement but showed earlier functioning recovery related to activities of daily living and reduced psychological distress. Routine distress screening is a promising mechanism to identify survivors with poorer health for more intensive supportive care.
Exact classical approach to the electron's self-energy and anomalous g-factor
Authors: Georgiev M.
Published: June 2024

An exact classical approach to the calculation of electron's self-energy and anomalous g-factor is reported. The electron's intrinsic dynamics, related electrodynamics and occurrence of anomalous magnetic moment are completely determined. A unique regularization of the electromagnetic field scalar potential underlying all results is derived. A fundamental transcendental equation satisfied by the electron's anomalous g-factor is obtained, with solution

, matching the experimentally measured value reported in the literature to 0.59 parts per trillion. Field representation of the electron intrinsic and orbital dynamics in atoms is discussed.
Machine Learning Reveals the Contribution of Lipoproteins to Liver Triglyceride Content and Inflammation
Authors: Tavaglione Federica , Marafioti Giuseppe , Romeo Stefano , Jamialahmadi Oveis
Published: June 2024

Context

Metabolic dysfunction–associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide and is strongly associated with metabolic comorbidities, including dyslipidemia.

Objective

Herein, we aim to estimate the prevalence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) in Europeans with isolated hypercholesterolemia and isolated hypertriglyceridemia in the UK Biobank and to estimate the independent contribution of lipoproteins to liver triglyceride content.

Methods

We selected 218 732 Europeans from the UK Biobank without chronic viral hepatitis and other causes of liver disease, of whom 14 937 with liver magnetic resonance imaging data available. Next, to examine the relationships between traits in predicting liver triglyceride content, we compared the predictive performance of several machine learning methods and selected the best performing algorithms based on the minimum cross-validated mean squared error (MSE).

Results

There was an approximately 3-fold and 4-fold enrichment of MASLD and MASH in individuals with isolated hypertriglyceridemia (P = 1.23 × 10–41 and P = 1.29 × 10–10, respectively), whereas individuals with isolated hypercholesterolemia had a marginal higher rate of MASLD and no difference in MASH rate compared with the control group (P = .019 and P = .97, respectively). Among machine learning methods, the feed-forward neural network had the best cross-validation MSE on the validation set. Circulating triglycerides, after body mass index, were the second strongest independent predictor of liver proton density fat fraction with the largest absolute mean Shapley additive explanation value.

Conclusion

Isolated hypertriglyceridemia is the second strongest, after obesity, independent predictor of MASLD/MASH. Individuals with hypertriglyceridemia, but not with hypercholesterolemia, should be screened for liver disease.
Teprotumumab for the Treatment of Thyroid Eye Disease
Authors: Ugradar Shoaib , Malkhasyan Emil , Douglas Raymond S
Published: June 2024

Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves’ disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED, chemosis, lid swelling, proptosis, and diplopia, are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that 1 of the major drivers of this molecular signature is the overexpression of the IGF-1 receptor [IGF-1R]) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human IgG1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the United States for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia, and burden on quality of life in patients who were treated. Postintroduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, more than 5800 patients have been treated with teprotumumab, and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first-line therapy for patients with moderate to severe TED who display features of proptosis and diplopia.
Interhemispheric and Corticothalamic White-Matter Dysfunction Underlies Affective Morbidity and Impaired Pain Modulation in Chronic Pain
Authors: Ito Atsushi , Yang Sushuang , Shinto Eri , Shinto Atsushi , Toyofuku Akira , Kurata Jiro
Published: June 2024

BACKGROUND:

Although patients with chronic pain show behavioral signs of impaired endogenous pain modulation, responsible cerebral networks have yet to be anatomically delineated. We used diffusion tensor imaging (DTI) to examine the white-matter alterations in patients with chronic pain compared with healthy subjects. We further measured thermal pain modulatory responses using the offset analgesia (OA) paradigm. We tested whether the white-matter indices be associated with psychophysical parameters reflecting morbidity and modulatory responses of pain in patients, and whether they could serve as diagnostic biomarkers of chronic pain.

METHODS:

Twenty-six patients with chronic pain and 18 age- and gender-matched healthy controls were enrolled. After completing psychophysical questionnaires, they underwent OA measurement and whole-brain DTI in a 3 Tesla magnetic resonance imaging scanner. Fractional anisotropy (FA) and radial diffusivity (RD) of the white-matter were computed and compared between the groups with tract-based spatial statistics using the FMRIB Software Library (FSL) software. Correlations were sought among white-matter indices, thermal pain responses, and psychophysical parameters. The white-matter indices and OA-related parameters were tested whether they distinguish patients from controls by receiver operating characteristic analysis.

RESULTS:

During OA, patients showed a shorter latency to the maximum (maximum visual analog scale [VAS] latency, 16.0 ± 3.7 vs 18.9 ± 3.1 second [mean ± standard deviation, SD]; P = .032) but a longer latency to the minimum pain (OA latency, 15.6 ± 3.5 vs 11.1 ± 4.2 seconds; P = .004) than controls. They showed a smaller mean FA (0.44 ± 0.12 vs 0.45 ± 0.11; P = .012) and a larger mean RD of the global white-matter (0.00057 ± 0.00002 vs 0.00056 ± 0.00002; P = .038) than controls, at specific areas including the corpus callosum, anterior thalamic radiation, and forceps major. FA of the splenium of the corpus callosum was associated with maximum VAS latency (r = 0.493) and OA latency (r = −0.552). The Pain Catastrophizing Scale scores showed strong negative correlations with FA across those specific areas (r = −0.405). Those latencies during OA and white-matter metrics distinguished patients from controls (P < .05).

CONCLUSIONS:

Patients with chronic pain showed dysfunction of the white matter concerned with interhemispheric communication of sensorimotor information as well as descending corticothalamic modulation of pain in association with affective morbidity and altered temporal dynamics of pain perception. We suggest that an impaired interhemispheric modulation of pain, through the corpus callosum, might be a novel cerebral mechanism in chronification of pain.
Regime Type and Data Manipulation: Evidence from the COVID-19 Pandemic
Authors: Wigley Simon
Published: June 2024

Context: This study examines whether autocratic governments are more likely than democratic governments to manipulate health data. The COVID-19 pandemic presents a unique opportunity for examining this question because of its global impact.

Methods: Three distinct indicators of COVID-19 data manipulation were constructed for nearly all sovereign states. Each indicator was then regressed on democracy and controls for unintended misreporting. A machine learning approach was then used to determine whether any of the specific features of democracy are more predictive of manipulation.

Findings: Democracy was found to be negatively associated with all three measures of manipulation, even after running a battery of robustness checks. Absence of opposition party autonomy and free and fair elections were found to be the most important predictors of deliberate undercounting.

Conclusions: The manipulation of data in autocracies denies citizens the opportunity to protect themselves against health risks, hinders the ability of international organizations and donors to identify effective policies, and makes it difficult for scholars to assess the impact of political institutions on population health. These findings suggest that health advocates and scholars should use alternative methods to estimate health outcomes in countries where opposition parties lack autonomy or must participate in uncompetitive elections.
Explaining Political Differences in Attitudes to Vaccines in France: Partisan Cues, Disenchantment with Politics, and Political Sophistication
Authors: Ward Jeremy K. , Cortaredona Sébastien , Touzet Hugo , Gauna Fatima , Peretti-Watel Patrick
Published: June 2024

Context: The role of political identities in determining attitudes to vaccines has attracted a lot of attention in the last decade. Explanations have tended to focus on the influence of party representatives on their sympathizers (partisan cues).

Methods: Four representative samples of the French adult population completed online questionnaires between July 2021 and May 2022 (N = 9,177). Bivariate and multivariate analyses were performed to test whether partisan differences in attitudes to vaccines are best explained by partisan cues or by parties’ differences in propensity to attract people who distrust the actors involved in vaccination policies.

Findings: People who feel close to parties on the far left, parties on the far right, and green parties are more vaccine hesitant. The authors found a small effect of partisan cues and a much stronger effect of trust. More importantly, they show that the more politically sophisticated are less vaccine hesitant and that the nonpartisan are the biggest and most vaccine hesitant group.

Conclusions: The literature on vaccine attitudes has focused on the case of the United States, but turning attention toward countries where disenchantment with politics is more marked helps researchers better understand the different ways trust, partisanship, and political sophistication can affect attitudes to vaccines.
Policy Feedback and the Politics of Childhood Vaccine Mandates: Conflict and Change in California, 2012–2019
Authors: Attwell Katie , Hannah Adam , Drislane Shevaun , Navin Mark Christopher
Published: June 2024

Context: In 2012, California instituted a new requirement for parents to consult with a clinician before receiving a personal belief exemption (PBE) to its school entry vaccine mandate. In 2015, the state removed this exemption altogether. In 2019, legislators cracked down on medical exemptions to address their misuse by vaccine refusers and supportive clinicians. This article uses “policy feedback theory” to explore these political conflicts, arguing that PBEs informed the emergence and approaches of two coalitions whose conflict reshaped California's vaccination policies.

Methods: The authors analyzed legal, policy, academic, and media documents; interviewed 10 key informants; and deductively analyzed transcripts using NVivo 20 transcription software.

Findings: California's long-standing vaccination policy inadvertently disseminated two fundamentally incompatible social norms: vaccination is a choice, and vaccination is not a choice. Over time, the culture and number of vaccine refusers grew, at least in part because the state's policy sanctioned the norm of vaccine refusal.

Conclusions: The long-term consequences of California's “mandate + PBE” policy—visible, public, and socially sanctioned vaccine refusal—undermined support for it over time, generating well-defined losses for a large group of people (the vaccinating public) and specifically for the provaccine parent activists whose experiences of personal grievance drove their mobilization for change.
The Role of Pelvic Compensation in Sagittal Balance and Imbalance: The Impact of Pelvic Compensation on Spinal Alignment and Clinical Outcomes Following Adult Spinal Deformity Surgery
Authors: Wang Zheng , Chen Xiaolong , Hu Xinli , Zhang Haojie , Zhu Weiguo , Wang Dongfan , Zhang Sitao , Kong Chao , Wang Wei , Lu Shibao
Published: June 2024

BACKGROUND AND OBJECTIVES:

The Scoliosis Research Society (SRS)-Schwab system does not include a pelvic compensation (PC) subtype, potentially contributing to gaps in clinical characteristics and treatment strategy for deformity correction. It also remains uncertain as to whether PC has differing roles in sagittal balance (SB) or imbalance (SI) status. To compare radiological parameters and SRS-22r domains between patients with failed pelvic compensation (FPC) and successful pelvic compensation (SPC) based on preoperative SB and SI.

METHODS:

A total of 145 adult spinal deformity patients who received deformity correction were analyzed. Radiographic and clinical outcomes were collected for statistical analysis. Patients were classified into 4 groups based on the median value of PT/PI ratio (PTr) and the cutoff value of SB. Patients with low PTr and high PTr were defined as FPC and SPC, respectively. Radiographic and clinical characteristics of different groups were compared.

RESULTS:

Patients with SPC exhibited significantly greater improvements in lumbar lordosis, pelvic tilt, PTr, and T1 pelvic angle as compared to patients with FPC, irrespective of SB or SI. No apparent differences in any of SRS-22r domains were observed at follow-up when comparing the SB-FPC and SB-SPC patients. However, patients with SI-SPC exhibited significantly better function, self-image, satisfaction, and subtotal domains at follow-up relative to those with SI-FPC. When SI-FPC and SI-SPC patients were subdivided further based on the degree of PI-LL by adjusting for age, the postoperative function and self-image domains were significantly better in the group with overcorrection of PI-LL than undercorrection of PI-LL in SI-FPC patients. However, no differences in these SRS-22r scores were observed when comparing the subgroups in SI-SPC patients.

CONCLUSION:

Flexible pelvic rotation is associated with benefits to the correction of sagittal parameters, irrespective of preoperative SB or SI status. However, PC is only significantly associated with clinical outcomes under SI. Patients with SI-FPC exhibit poorer postoperative clinical outcomes, which should be recommended to minimize PI-LL.
Rates and Predictors of Pain Reduction With Intracranial Stimulation for Intractable Pain Disorders
Authors: Huang Yuhao , Sadeghzadeh Sina , Li Alice Huai-Yu , Schonfeld Ethan , Ramayya Ashwin G. , Buch Vivek P.
Published: June 2024

BACKGROUND AND OBJECTIVES:

Intracranial modulation paradigms, namely deep brain stimulation (DBS) and motor cortex stimulation (MCS), have been used to treat intractable pain disorders. However, treatment efficacy remains heterogeneous, and factors associated with pain reduction are not completely understood.

METHODS:

We performed an individual patient review of pain outcomes (visual analog scale, quality-of-life measures, complications, pulse generator implant rate, cessation of stimulation) after implantation of DBS or MCS devices. We evaluated 663 patients from 36 study groups and stratified outcomes by pain etiology and implantation targets.

RESULTS:

Included studies comprised primarily retrospective cohort studies. MCS patients had a similar externalized trial success rate compared with DBS patients (86% vs 81%; P = .16), whereas patients with peripheral pain had a higher trial success rate compared with patients with central pain (88% vs 79%; P = .004). Complication rates were similar for MCS and DBS patients (12% vs 15%; P = .79). Patients with peripheral pain had lower likelihood of device cessation compared with those with central pain (5.7% vs 10%; P = .03). Of all implanted patients, mean pain reduction at last follow-up was 45.8% (95% CI: 40.3-51.2) with a 31.2% (95% CI: 12.4-50.1) improvement in quality of life. No difference was seen between MCS patients (43.8%; 95% CI: 36.7-58.2) and DBS patients (48.6%; 95% CI: 39.2-58) or central (41.5%; 95% CI: 34.8-48.2) and peripheral (46.7%; 95% CI: 38.9-54.5) etiologies. Multivariate analysis identified the anterior cingulate cortex target to be associated with worse pain reduction, while postherpetic neuralgia was a positive prognostic factor.

CONCLUSION:

Both DBS and MCS have similar efficacy and complication rates in the treatment of intractable pain. Patients with central pain disorders tended to have lower trial success and higher rates of device cessation. Additional prognostic factors include anterior cingulate cortex targeting and postherpetic neuralgia diagnosis. These findings underscore intracranial neurostimulation as an important modality for treatment of intractable pain disorders.
Resting State Functional Networks in Gliomas: Validation With Direct Electric Stimulation Using a New Tool for Planning Brain Resections
Authors: Moretto Manuela , Luciani Beatrice Federica , Zigiotto Luca , Saviola Francesca , Tambalo Stefano , Cabalo Donna Gift , Annicchiarico Luciano , Venturini Martina , Jovicich Jorge , Sarubbo Silvio
Published: June 2024

BACKGROUND AND OBJECTIVES:

Precise mapping of functional networks in patients with brain tumor is essential for tailoring personalized treatment strategies. Resting-state functional MRI (rs-fMRI) offers an alternative to task-based fMRI, capable of capturing multiple networks within a single acquisition, without necessitating task engagement. This study demonstrates a strong concordance between preoperative rs-fMRI maps and the gold standard intraoperative direct electric stimulation (DES) mapping during awake surgery.

METHODS:

We conducted an analysis involving 28 patients with glioma who underwent awake surgery with DES mapping. A total of 100 DES recordings were collected to map sensorimotor (SMN), language (LANG), visual (VIS), and speech articulation cognitive domains. Preoperative rs-fMRI maps were generated using an updated version of the ReStNeuMap software, specifically designed for rs-fMRI data preprocessing and automatic detection of 7 resting-state networks (SMN, LANG, VIS, speech articulation, default mode, frontoparietal, and visuospatial). To evaluate the agreement between these networks and those mapped with invasive cortical mapping, we computed patient-specific distances between them and intraoperative DES recordings.

RESULTS:

Automatically detected preoperative functional networks exhibited excellent agreement with intraoperative DES recordings. When we spatially compared DES points with their corresponding networks, we found that SMN, VIS, and speech articulatory DES points fell within the corresponding network (median distance = 0 mm), whereas for LANG a median distance of 1.6 mm was reported.

CONCLUSION:

Our findings show the remarkable consistency between key functional networks mapped noninvasively using presurgical rs-fMRI and invasive cortical mapping. This evidence highlights the utility of rs-fMRI for personalized presurgical planning, particularly in scenarios where awake surgery with DES is not feasible to protect eloquent areas during tumor resection. We have made the updated tool for automated functional network estimation publicly available, facilitating broader utilization of rs-fMRI mapping in various clinical contexts, including presurgical planning, functional reorganization over follow-up periods, and informing future treatments such as radiotherapy.
Iliotibial Band Origin Tendinopathy Is an Underrecognized Cause of Anterolateral Hip Pain: A Narrative Review and Clinical Commentary
Authors: Buttinger Jessica N. , Romero Joshua M. , Sellon Jacob L. , Lachman Nirusha , Kruse Ryan C. , Boettcher Brennan J.
Published: June 2024

Hip pain is a common concern among athletes. With gluteal tendinopathy, femoroacetabular impingement, and osteoarthritis predominating sports medicine and musculoskeletal practices, less common etiologies may be overlooked. Complex pelvic anatomy and variable pain referral patterns may make identifying an accurate diagnosis challenging. Employing a systematic approach to evaluation and having a thorough understanding of hip region anatomy are essential. A potentially overlooked cause of anterolateral hip pain is iliotibial band origin tendinopathy. Patients often present with pain around the anterolateral hip and tenderness to palpation at the anterolateral iliac crest. While patients with iliotibial band origin tendinopathy usually respond to nonsurgical intervention, there is little literature to guide evaluation and treatment, highlighting a gap in the recognition of this condition. The purpose of this narrative review is to describe the anatomy of the proximal iliotibial band origin, outline the clinical diagnosis and imaging findings of ITBOT, and summarize current treatment options.
Gluteus Maximus Distal Myotendinous Junction Tear in a Pickleball Player: A Case Report
Authors: King Shanterian , Johnson Adam , Jelsing Elena
Published: June 2024

A 72-year-old male presented for evaluation of a 2-wk history left buttock pain that began while playing pickleball. He sustained a left inversion ankle sprain while in a squatted position and landed on his left buttock. Four days after his injury, he developed extensive bruising involving his lower back, buttock, and left thigh. On examination, he had tenderness to palpation at the left side of the sacrum and in the region of the deep external rotators. Left hip range of motion was full in extension but limited to 90° of flexion, which reproduced left-sided buttock pain. External rotation provoked pain, but internal rotation was full and pain free. MRI of the pelvis demonstrated a grade 2 partial thickness tear of the left gluteus maximus muscle at its distal myotendinous junction with associated retraction and intramuscular hematoma. He was managed with compression with biking shorts, icing, acetaminophen, and physical therapy. He returned to pickleball approximately 4 wk after his injury, and at his 4-wk follow-up, he reported 99% improvement in his symptoms with the only remaining complaint being minimal discomfort with gluteal stretching.
Function and mechanism of action of the small regulatory RNA ArcZ inEnterobacterales
Authors: Dubois Quentin , Brual Typhaine , Oriol Charlotte , Mandin Pierre , Condemine Guy , Gueguen Erwan
Published: June 2024

ArcZ is a small regulatory RNA conserved inEnterobacterales. It is an Hfq-dependent RNA that is cleaved by RNase E in a processed form of 55–60 nucleotides. This processed form is highly conserved for controlling the expression of target mRNAs. ArcZ expression is induced by abundant oxygen levels and reaches its peak during the stationary growth phase. This control is mediated by the oxygen-responsive two-component system ArcAB, leading to the repression ofarcZtranscription under low-oxygen conditions in most bacteria in which it has been studied. ArcZ displays multiple targets, and it can control up to 10% of a genome and interact directly with more than 300 mRNAs inEscherichia coliandSalmonella enterica. ArcZ displays a multifaceted ability to regulate its targets through diverse mechanisms such as RNase recruitment, modulation of ribosome accessibility on the mRNA, and interaction with translational enhancing regions. By influencing stress response, motility, and virulence through the regulation of master regulators such as FlhDC or RpoS, ArcZ emerges as a major orchestrator of cell physiology withinEnterobacterales.
From ‘village tanks’ to ‘evaporating pans’: Colonial and Post-colonial responses to ancient village tanks in Sri Lanka
Authors: Jayawardana Chandana , Sadeepa H D Dilini
Published: June 2024

Village tanks, prevalent since ancient times, were an integrated part of the irrigation system in Sri Lanka (‘Ceylon’ till 1972). It was under these village tanks that paddy cultivation took place, and they were a part of the socially, technologically, and ecologically cohesive way of village life. The colonial authorities, who tried to renovate that ancient system, perceived village tanks as technically inefficient due to excessive evaporation and uneconomical land use. However, for several reasons, that perception could not be materialized during their renovation works. During the post-colonial period, with the implementation of the land colonization schemes in the 1930’s and the multipurpose river valley development schemes in the 1960’s, the scenario took a different shape. The technically perceived inferiority of the village tanks was brought into the new water management policies and the engineering designs. As a result, many of the village tanks were demolished, and those lands were converted to the farmlands. Instead of water availabilities assured through village tanks, canal irrigation became prominent. The socio-technical bondage between the village tanks and the village communities was not considered, presenting a classic case study for the consequences of neglecting social component of the technology. This paper discusses the social, political, and technical implications of these moves and their influence on shaping the present irrigation setup in the island.
Effectiveness of vestibular rehabilitation therapy and yoga in the management of chronic peripheral vertigo: A randomized controlled trial
Authors: Vaishali K. , Kishore Chandra Prasad , Sampath Chandra Prasasd Rao , P. S. Jeganathan
Published: June 2024

Background The purpose of the study was to compare the effectiveness of yoga as a form of Vestibular Rehabilitation (VR) to standard VR for managing patients with symptoms such as dizziness, disequilibrium and gait instability. Methods 150 participants based on 18-point difference in the DHI score were randomly assigned to group 1- Yoga, group 2- VR and group 3- control group using block randomization. The intervention was provided for 12 weeks. The participants were assessed for Dizziness Handicap Inventory (DHI) at baseline, 4th, 8th and 12th week. Results The mean DHI for group 1(41.12±7.13) group 2 (42.96±10.54) group 3 (50.84±10.78), p<0.001 decreased significantly in group 1 and 2 when compared to baseline. There was no statistically significant difference in overall Dizziness Handicap Inventory (DHI) scores between the Yoga and Physiotherapy groups after one month; however, both groups resulted in a significant decrease in scores when compared to the control group. Similarly, by the end of the second and third months, there was no significant distinction between the Yoga and Physiotherapy groups, even though both had a considerable decrease in DHI scores when compared to the control group. Furthermore, an examination of the functional, emotional, and physical components of DHI demonstrated persistent trends of significant improvement in both the Yoga and Physiotherapy groups as compared to the control group over a three-month period. Conclusions In addition to VR, Yoga and medications administered concurrently can provide effective therapeutic effects. Yoga has an advantage over VR since it offers a customized cure for giddiness in addition to symptom relief. Yoga might be a great alternative to the conventional VR because along with enhancing overall body relaxation, it is affordable and is easy to learn.
The Impact of Cardiac Rehabilitation on Psychosocial Factors, Functional Capacity, and Left Ventricular Function in Patients with Coronary Artery Disease: Systematic Review and Meta-Analysis
Authors: Harbi Ali Suleiman , Soh Dr Kim Lam , Yubbu Dr Putri Binti , Soh Kim Geok
Published: June 2024

Background Cardiac rehabilitation is a multifaceted program implemented after adverse events. It aims at facilitating the return to normal life. This review aimed to examine the impact of cardiac rehabilitation on psychosocial risk factors, functional capacity, and left ventricular function. Methods The following databases: CINAHL, Scopus, PubMed, and Cochrane Library have been searched to retrieve the randomized controlled trials that investigate the effectiveness of cardiac rehabilitation versus usual care on anxiety, depression, peak oxygen consumption, six-minute walk distance, left ventricular ejection fraction, and left ventricular end-systolic and diastolic dimensions. Filters were set to retrieve trials that were published in the English Language between 2000 and 2024. Risk of bias was assessed using the Cochrane risk-of-bias tool (Rob2). Data were analysed meta-analytically. Results Twenty two (22) trials were included, randomized 2283 participants. A significant improvement favouring intervention groups was observed in anxiety SMD = -0.3890 (95% CI: -0.5640 to -0.2140; p˂0.001), depression SMD = -0.4032 (95% CI: -0.7114 to -0.0950; p= 0.002), peak oxygen consumption MD = 1.2471 (95% CI: 0.3963 to 2.0979; p = 0.004), six-minute walk distance MD = 36.0290 (95% CI: 7.7497 to 64.3082; p = 0.013), and left ventricular ejection fraction MD = 3.0650 (95% CI: 1.1279 to 5.0022; p = 0.001), Although cardiac rehabilitation had no significant effect in decreasing left ventricular end-diastolic dimension MD = -0.0480 (95% CI: -0.2609 to 0.1648; p = 0.658) and left ventricular end-systolic and MD = -0.0670 (95% CI: -0.2829 to 0.1489; p = 0.543) a favourable trend toward intervention group was seen. Risk of bias was high in 1 study and unclear in 7 studies. Conclusion For patients with Coronary Artery Disease, cardiac rehabilitation demonstrated effectiveness in improving psychological symptoms such as anxiety and depression, functional capacity as measured by peak oxygen consumption and six-minute walk test, and left ventricular function.
Expectations and Vietnam’s responses during COVID-19: potential human rights violations and related propositions
Authors: Doan Hai
Published: June 2024

Background It appears that underneath many propositions or actions, there might have been certain expectations. The reality of the complexity of human beings and interactions within a society yields expectations which, in turn, further interact with each other. Methods This paper offers the first in-depth study on ‘expectations’ in bioethical and health law studies, taking Vietnam’s responses to coronavirus disease (COVID-19) as an illustration. Results It defines ‘expectations’ as normative imaginaries that can induce or guide actions and inactions at individual and collective levels. Conclusions It argues that violations of human rights and certain related propositions within the Vietnamese context can be understood in terms of expectations. Within such contexts as Vietnam, expectations account for behaviours, including human rights violations. It suggests that ‘expectations’ is a fruitful concept for bioethical and health law studies. Studying expectations thus has implications for governance and future research agendas.