bluuebunny/crossref_metadata_2025 huggingface dataset:
FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models
Authors: Guo Qingsong , Gao Bei , Song Ruiwen , Li Weinan , Zhu Shulei , Xie Qian , Lou Sensen , Wang Lei , Shen Jiafei , Zhao Teng , Zhang Yifan , Wu Jinsong , Lu Wei , Yang Tong
Published: June 2024

Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody–drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine. In this study, we developed a novel DLL3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody, FZ-A038, and a valine–alanine (Val–Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line–derived xenograft and patient-derived xenograft models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable, and the highest nonseverely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of patients with SCLC.
Tumor Microenvironment Reprogramming Improves Nanomedicine-Based Chemo-Immunotherapy in Sarcomas
Authors: Charalambous Antonia , Mpekris Fotios , Panagi Myrofora , Voutouri Chrysovalantis , Michael Christina , Gabizon Alberto A. , Stylianopoulos Triantafyllos
Published: June 2024

Sarcomas are a heterogeneous group of rare cancers that originate in soft tissues or bones. Their complexity and tendency for metastases make treatment challenging, highlighting the need for new therapeutic approaches to improve patient survival. The difficulties in treating these cancers primarily stem from abnormalities within the tumor microenvironment (TME), which leads to reduced blood flow and oxygen levels in tumors. Consequently, this hampers the effective delivery of drugs to tumors and diminishes treatment efficacy despite higher toxic doses of chemotherapy. In this study, we tested the mechanotherapeutic ketotifen combined with either pegylated liposomal doxorubicin (PLD) or pegylated liposomal coencapsulated alendronate–doxorubicin (PLAD) plus anti–programmed cell death protein 1 antibody in mouse models of fibrosarcoma and osteosarcoma. We found that ketotifen successfully reprogrammed the TME by reducing tumor stiffness and increasing perfusion, proven by changes measured by shear-wave elastography and contrast-enhanced ultrasound, respectively, and enhanced the therapeutic efficacy of our nanomedicine-based chemo-immunotherapy protocols. Furthermore, we observed a trend toward improved antitumor responses when nano-chemotherapy is given alongside anti–programmed cell death protein 1 and when the immunomodulator alendronate was present in the treatment. We next investigated the mechanisms of action of this combination. Ketotifen combined with nanomedicine-based chemo-immunotherapy increased T-cell infiltration, specifically cytotoxic CD8+ T cells and CD4+ T helper cells, and decreased the number of regulatory T cells. In addition, the combination also altered the polarization of tumor-associated macrophages, favoring the M1 immune-supportive phenotype over the M2 immunosuppressive phenotype. Collectively, our findings provide evidence that ketotifen-induced TME reprogramming can improve the efficacy of nanomedicine-based chemo-immunotherapy in sarcomas.
FIGURE 2 from First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study
Authors: Wheatley Duncan A. , Berardi Rossana , Climent Duran Miguel A. , Tomiak Anna , Greystoke Alastair P. , Joshua Anthony M. , Arkenau Hendrik-Tobias , Géczi Lajos , Corbacho Javier Garciá , Paz-Ares Luis G. , Hussain Syed A. , Petruželka Lubos , Delmonte Angelo , Chappey Colombe , Masters Joanna C. , Michelon Elisabete , Murphy Danielle A. , Mwewa Sandrine , Cesari Rossano , Doger de Spéville Bernard
Published: June 2024

Pharmacokinetics of avelumab over time following administration of 800 and 1,200 mg every 3 weeks in the urothelial carcinoma and NSCLC cohorts. A, Serum avelumab Ctrough by visit. B, Serum avelumab Cmax by visit. C, Serum avelumab concentrations on day 15 visit. Horizontal black line within each box depicts the median, and upper and lower lines depict the third (Q3) and first (Q1) quantiles, respectively. Upper and lower error bars represent Q3 + 1.5 × IQR and Q1 – 1.5 × IQR, respectively. Dashed line represents median, and dotted lines represent 5th and 95th percentiles of historical steady state Ctrough (A and C) or Cmax (B) from population pharmacokinetic model–based simulations of avelumab 10 mg/kg every 2 weeks in monotherapy (1, 2). IQR, interquartile range.
A Phone in a Basket Looks Like a Knife in a Cup: Role-Filler Independence in Visual Processing
Authors: Hafri Alon , Bonner Michael F. , Landau Barbara , Firestone Chaz
Published: June 2024

When a piece of fruit is in a bowl, and the bowl is on a table, we appreciate not only the individual objects and their features, but also the relations containment and support, which abstract away from the particular objects involved. Independent representation of roles (e.g., containers vs. supporters) and “fillers” of those roles (e.g., bowls vs. cups, tables vs. chairs) is a core principle of language and higher-level reasoning. But does such role-filler independence also arise in automatic visual processing? Here, we show that it does, by exploring a surprising error that such independence can produce. In four experiments, participants saw a stream of images containing different objects arranged in force-dynamic relations—e.g., a phone contained in a basket, a marker resting on a garbage can, or a knife sitting in a cup. Participants had to respond to a single target image (e.g., a phone in a basket) within a stream of distractors presented under time constraints. Surprisingly, even though participants completed this task quickly and accurately, they false-alarmed more often to images matching the target’s relational category than to those that did not—even when those images involved completely different objects. In other words, participants searching for a phone in a basket were more likely to mistakenly respond to a knife in a cup than to a marker on a garbage can. Follow-up experiments ruled out strategic responses and also controlled for various confounding image features. We suggest that visual processing represents relations abstractly, in ways that separate roles from fillers.
Cretaceous beetles of the Jinju Formation (Coleoptera: Hydrophiloidea)
Authors: LEE SOO-BIN , CAI CHEN-YANG , ENGEL MICHAEL S. , NAM GI-SOO , PARK JONG-KYUN
Published: June 2024

We report new discoveries of diverse Hydrophiloidea (Staphyliniformia) from the Albian (Early Cretaceous) Jinju Formation, South Korea, including the genera Laetopsia Fikáček et al., 2012 and Cretotaenia Ponomarenko, 1977, a new species of Laetopsia (Laetopsia leei sp. nov.), a species putatively shared with the Barremian Yixian Formation of China (L. cf. hydraenoides), an undetermined species of Laetopsia, and a new record of Cretotaenia pallida Ponomarenko are described and illustrated.
The first fossil mantis lacewing (Neuroptera: Mantispidae) from Australia
Authors: HART LACHLAN J. , ENGEL MICHAEL S. , FRESE MICHAEL , MCCURRY MATTHEW R.
Published: June 2024

Mantispidae is a cosmopolitan family of neuropteran insects, with approximately 395 extant species (Ohl et al., 2004; Jepson, 2015; Engel et al., 2018; Li et al., 2023). The family includes some of the most distinctive of lacewings owing to their convergent traits with mantises (Mantodea), complete with elongate prothoraces, prominent and large compound eyes on a moveable head, and powerful raptorial forelegs. Indeed, species of the family are referred to as mantis lacewings or mantid lacewings owing to the considerable similarity. As one would suspect, adults are predatory on a variety of small-bodied arthropods, typically hunting during dusk or night (Snyman et al., 2020). Larvae are also predators, although some are specialised for particular prey (e.g., subfamily Symphrasinae), while those of the nominate subfamily Mantispinae are ectoparasitic on spider egg cases (Redborg, 1998). Extant Mantispidae are found on every continent except Antarctica but show their highest diversity and geographical distribution in Australia and the Americas (Fig. 1A).
Gomphocopris ashworthi gen. et sp. nov. (Coleoptera, Scarabaeinae, Homocoprini): An additional new Chilean fossil genus and species extinct at the Pleistocene-Holocene boundary
Authors: TELLO FRANCISCO , GÉNIER FRANÇOIS , PINO MARIO , ROSSINI MICHELE , VERDÚ JOSÉ R.
Published: June 2024

Based on male and female fossil beetle remains recorded in the Pilauco deposits (northern Chilean Patagonia), a new and extinct dung beetle genus and species from an upper Pleistocene sequence (16.4 to 12.8 kyr BP) namely, Gomphocopris ashworthi gen. et sp. nov. (Coleoptera, Scarabaeidae, Homocoprini) is described and illustrated. The morphological analysis of these fossil remains suggest that this extinct genus and species are placed into the tribe Homocoprini due to presence of supplementary carina in the lateral area in the pronotum. Moreover, this new taxon is separated from the extant Homocoprini species by the absence hypomeral carina (well developed in all extant species); cephalic horn in males with a distinct posterior projection apically (absent in the extant species), and the unique shapes and disposition of the pronotal lobes in major male and female. We suggest that this dung beetle genus and species became extinct in the late Pleistocene to early Holocene as a consequence of the drastic environmental changes, and the extinction of most of the large mammals, which were the organisms that provided feces for the development of their larvae.
The Risk Factors of Low Birth Weight in Primary Health Care Centres: A Comparative Study in Selected Rural and Urban Settings in a Southwestern State of Nigeria
Authors: Daniel Ebenezer , Olawale Oluseyi , Bello Ahmed , Avwerhota Michael , Tomori Michael , Popoola Israel , Adetutu Adebanke , Salami Aisha , Alewi Olukayode , Popoola Taiwo , Ekwuluo Celestine
Published: June 2024

The World Health Organization (WHO) defines low birth weight (LBW) as less than 2500g at birth, a critical predictor of infant morbidity and mortality. LBW prevalence is notably higher in developing countries (15%) compared to developed ones (7%), affecting 5–6 million children annually in Nigeria. This study aimed to identify and compare LBW risk factors in rural and urban areas of Ondo State, Nigeria, and to describe the socio-demographic and pregnancy characteristics of affected mothers. Conducted from January 2021 to August 2022, the case-control study analyzed live birth records from selected primary health centers. Factors such as socio-demographics, anthropometrics, nutrition, maternal morbidity, and antenatal care were considered. Logistic regression models, both bivariate and multivariate, were used to analyze the data. The study found a LBW incidence of 10.2%, with 9.7% in rural and 11% in urban areas. BMI, maternal age, occupation, and marital status were not correlated with LBW. In urban areas, lower parity and frequent medication use during pregnancy were linked to lower LBW risk, while ANC visits significantly impacted LBW incidence (p < 0.05). Overall, ANC visits, iron supplement use, and parity were significant LBW risk factors, particularly in urban settings, whereas socio-demographic factors showed no substantial association.
Optimizing Growth Regulators for Micropropagation of Industrially Adaptable Eucalyptus Hybrids
Authors: Naickar Malaimuthu , Palanisamy Chezhian , Vazram Prasath , Kuppusamy Jayakumar , Thangavel Stalin , Ramasamy Rajesh
Published: June 2024

Eucalyptus is one of the highly economic tree species in the developing countries like India. In the present investigation, experiments on optimizing plant growth regulators in the micropropagation of promising inter specific Eucalyptus hybrid clones namely TNPL 191(E. camaldulensis× E. teriticornis), TNPL 192 (E. camaldulensis × E. pellita) and intra specific hybrid clone TNPL 193 (E. camaldulensis× E. camaldulensis) were conducted, following standard protocols developed for Eucalyptus. The results showed that the BAP concentration of 0.50 mg L-1 for bud induction, IAA concentration of 3.0 mg L-1 for shoot elongation and IBA concentration of 1.0 mg L-1 for rooting of all these clones were found optimal. However, these three hybrid clones responded differently to the concentration of BAP at shoot proliferation stage. While the hybrid TNPL 191 showed maximum shoot proliferation rate at the concentration of 0.2 mg L-1 of BAP, the hybrids TNPL 192 and TNPL 193 showed highest response at 0.15 mg L-1. All the in vitro rooted plantlets were acclimatized successfully to the prevailing natural environment. Thus, the protocols developed with respect to optimizing the plant growth regulators can be adapted in large scale micro propagation of inter and intra specific Eucalyptus hybrid clones.
Climate Change Impacts on Maritime Resources in Lebanon Using Satellites Imagery, Chekka Case Study
Authors: Ghiye Sirine
Published: June 2024

This paper aims to explore the impact of climate change on underwater and coastal sites over the past few decades, with a specific focus on the Chekka area in North Lebanon. Given its rich maritime archaeology potential, this region has become a focal point, especially with the ongoing developments posing a threat to cultural resources. Detecting climate changes necessitates extensive measurements from various sources globally, including land stations, ships, and satellite imagery. In this study, we concentrate on changes in sea surface temperature (SST) over the last 20 to 40 years. The analysis heavily relies on satellite imagery, with a primary focus on Landsat 8, equipped with two bands of the thermal infrared sensor (TIRS), and Landsat 7, which carries the Enhanced Thematic Mapper Plus (ETM+) sensor, and also Landsat 5 TM. Utilizing QGIS for the calculation of SST, our findings reveal a noteworthy increase of 1° in sea surface temperature over the past two decades. This observation underscores the significance of ongoing climate change and its potential repercussions for the underwater and coastal cultural heritage in the Chekka area and its suburbs.
Meaningful Peer Social Interactions and Momentary Well-Being in Context
Authors: Roshanaei Mahnaz , Vaid Sumer S. , Courtney Andrea L. , Soh Serena J. , Zaki Jamil , Harari Gabriella M.
Published: June 2024

Using three large-scale longitudinal datasets collected from a cohort of university students over the span of 3 years (total N = 2,896 participants; ecological momentary assessments = 129,414), we found that engagement in meaningful social interactions with peers was associated with lower momentary loneliness and greater affective well-being. We also examined the role of four contextual factors (interaction partners, communication channels, places, and co-occurring activities) in explaining the relationships between meaningful social interactions and momentary well-being. Across samples, we found (a) participants reported experiencing greater loneliness and lower affective well-being after engaging in meaningful social interaction via computer-mediated channels (and via direct messaging in particular), compared to face-to-face, and (b) participants reported experiencing lower affective well-being after engaging in meaningful social interactions while dining and studying or working, compared to while resting. Taken together, our findings provide insight into the relationships between meaningful social interactions, momentary well-being, and contextual factors.
Optimizing drug combinations for T-PLL: restoring DNA damage and P53-mediated apoptotic responses
Authors: von Jan Jana , Timonen Sanna , Braun Till , Jiang Qu , Ianevski Aleksandr , Peng Yayi , McConnell Kathleen , Sindaco Paola , Müller Tony Andreas , Pützer Sabine , Klepzig Hanna , Jungherz Dennis , Dechow Annika , Wahnschaffe Linus , Giri Anil K. , Kankainen Matti , Kuusanmäki Heikki , Neubauer Heidi A. , Moriggl Richard , Mazzeo Paolo , Schmidt Nicole , Koch Raphael , Hallek Michael , Chebel Amel , Armisen David , Genestier Laurent , Bachy Emmanuel , Mishra Anjali , Schrader Alexandra , Aittokallio Tero , Mustjoki Satu , Herling Marco
Published: June 2024

T-prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm associated with marked chemotherapy resistance and continued poor clinical outcomes. Current treatments, that is, the CD52-antibody alemtuzumab, offer transient responses, with relapses being almost inevitable without consolidating allogeneic transplantation. Recent more detailed concepts of T-PLL’s pathobiology fostered the identification of actionable vulnerabilities: (1) altered epigenetics, (2) defective DNA damage responses, (3) aberrant cell-cycle regulation, and (4) deregulated prosurvival pathways, including T-cell receptor and JAK/STAT signaling. To further develop related preclinical therapeutic concepts, we studied inhibitors of histone deacetylases ([H]DACs), B-cell lymphoma 2 (BCL2), cyclin-dependent kinase (CDK), mouse double minute 2 (MDM2), and classical cytostatics, using (1) single-agent and combinatorial compound testing in 20 well-characterized and molecularly profiled primary T-PLL (validated by additional 42 cases) and (2) 2 independent murine models (syngeneic transplants and patient-derived xenografts). Overall, the most efficient/selective single agents and combinations (in vitro and in mice) included cladribine, romidepsin ([H]DAC), venetoclax (BCL2), and/or idasanutlin (MDM2). Cladribine sensitivity correlated with expression of its target RRM2. T-PLL cells revealed low overall apoptotic priming with heterogeneous dependencies on BCL2 proteins. In additional 38 T-cell leukemia/lymphoma lines, TP53 mutations were associated with resistance toward MDM2 inhibitors. P53 of T-PLL cells, predominantly in wild-type configuration, was amenable to MDM2 inhibition, which increased its MDM2-unbound fraction. This facilitated P53 activation and downstream signals (including enhanced accessibility of target-gene chromatin regions), in particular synergy with insults by cladribine. Our data emphasize the therapeutic potential of pharmacologic strategies to reinstate P53-mediated apoptotic responses. The identified efficacies and their synergies provide an informative background on compound and patient selection for trial designs in T-PLL.
Immune modulation permits tolerance and engraftment in a murine model of late-gestation transplantation
Authors: Riley John S. , Berkowitz Cara L. , Luks Valerie L. , Dave Apeksha , Cyril-Olutayo Mojisola C. , Pogoriler Jennifer , Flake Alan W. , Abdulmalik Osheiza , Peranteau William H
Published: June 2024

In utero hematopoietic cell transplantation is an experimental nonmyeloablative therapy with potential applications in hematologic disorders, including sickle cell disease (SCD). Its clinical utility has been limited due to the early acquisition of T-cell immunity beginning at ∼14 weeks gestation, posing significant technical challenges and excluding treatment fetuses evaluated after the first trimester. Using murine neonatal transplantation at 20 days postcoitum (DPC) as a model for late-gestation transplantation (LGT) in humans, we investigated whether immune modulation with anti-CD3 monoclonal antibody (mAb) could achieve donor-specific tolerance and sustained allogeneic engraftment comparable with that of the early-gestation fetal recipient at 14 DPC. In allogeneic wild-type strain combinations, administration of anti-CD3 mAb with transplantation resulted in transient T-cell depletion followed by central tolerance induction confirmed by donor–specific clonal deletion and skin graft tolerance. Normal immune responses to third-party major histocompatibility complex and viral pathogens were preserved, and graft-versus-host disease did not occur. We further demonstrated the successful application of this approach in the Townes mouse model of SCD. These findings confirm the developing fetal T-cell response as a barrier to LGT and support transient T-cell depletion as a safe and effective immunomodulatory strategy to overcome it.
Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Authors: Bewersdorf Jan Philipp , Shimony Shai , Shallis Rory M. , Liu Yiwen , Berton Guillaume , Schaefer Eva J. , Zeidan Amer M. , Goldberg Aaron D. , Stein Eytan M. , Marcucci Guido , Bystrom Rebecca P. , Lindsley R. Coleman , Chen Evan C. , Ramos Perez Jorge , Stein Anthony , Pullarkat Vinod , Aldoss Ibrahim , DeAngelo Daniel J. , Neuberg Donna S. , Stone Richard M. , Garciaz Sylvain , Ball Brian , Stahl Maximilian
Published: June 2024

Although intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), hypomethylating agents + venetoclax (HMA/VEN) can lead to durable remission among older patients with nucleophosmin 1 (NPM1) mutations. Whether IC or HMA/VEN is superior in patients aged ≥60 years with NPM1-mutant AML is unknown. We performed an international, multicenter retrospective cohort study of 221 patients (147 IC and 74 HMA/VEN) with previously untreated NPM1-mutant AML. Composite complete remission (cCR) (defined as CR + CR with incomplete count recovery) rate was similar for IC and HMA/VEN (cCR, 85% vs 74%; P = .067). Although overall survival (OS) was favorable with IC in unselected patients compared with HMA/VEN (24-month OS, 59% [95% confidence interval (CI), 52-69%] vs 38% [95% CI, 27-55%]; P = .013), it was not statistically different among patients aged 60-75 years (60% [95% CI, 52-70%] vs 44% [95% CI, 29-66%]; P = .069) and patients who received an allogeneic stem cell transplant (70% [95% CI, 58-85%] vs 66% [95% CI, 44-100%]; P = .56). Subgroup analyses suggested that patients with normal cytogenetics (24-month OS, 65% [95% CI, 56-74%] with IC vs 40% [95% CI, 26-60%] with HMA/VEN; P = .009) and without FLT3 internal tandem duplication mutations might benefit from IC compared with HMA/VEN (24-month OS, 68% [95% CI, 59-79%] vs 43% [95% CI, 29-63%]; P = .008). In multivariable analysis, OS was not statistically different between patients treated with IC and HMA/VEN (hazard ratio for death with HMA/VEN vs IC, 0.71; 95% CI, 0.40-1.27; P = .25).
Physical activity dynamically moderates the impact of multimorbidity on the trajectory of healthy aging over sixteen years
Authors: Ojijieme Nnaelue Godfrey , Feng Tieying , Chui Chin Man , Qi Xinzhu , Liu Yuan
Published: June 2024

Background

Research examining the healthy aging trajectory of retired older adults with multimorbidity is limited, leaving uncertainties regarding the optimal physical activity (PA) intensity and frequency necessary to sustain healthy aging during retirement.

Methods

Our study investigated the moderating effects of PA on the healthy aging trajectories of retired older adults living with multimorbidity in the United States (US). We utilized data from 1,238 retired individuals aged 50 to 102 who contributed 11,142 observations over 16 years from the Health and Retirement Study (HRS). We employed mixed effects modeling to assess the impact of various classes of multimorbidity on this group and examine how different PA, PA intensities, and PA frequencies influence the disability, physical, and cognitive functioning domains of healthy aging.

Results

The results reveal that while outcomes differed significantly, retired older adults in the US attained healthy aging at baseline. However, their ability to maintain healthy aging declined over time, with multimorbidity, especially musculoskeletal and neurological conditions, accelerating this decline. Fortunately, PA, especially light to moderate intensities, is associated with improving healthy aging and moderating the impact of multimorbidity on the disability and cognitive functioning domains of healthy aging. However, the specific moderating effects of PA depend on its frequency, intensity, and chronic conditions.

Conclusions

The significant variability in healthy aging attainment among retired older adults underlies the need to consider these differences when addressing healthy aging issues in the US. Accounting for these variations would aid in evaluating the potential impact of future interventions and contribute to achieving health equity. Fortunately, our dynamic findings facilitate this objective by identifying specific frequencies and intensities of PA tailored to different aspects of multimorbidity and healthy aging. This highlights PA, especially light-to-moderate intensity, as an essential, cost-effective, and amenable strategy for alleviating the impact of multimorbidity on healthy aging.
Factors influencing participation and regular attendance in a program combining physical activity and nutritional advice for overweight and obese pregnant women
Authors: Lelorain Sophie , Deruelle Philippe , Béhal Hélène , Machet Elise , Thiblet Marie , Lengagne-Piedbois Christelle , Deken-Delannoy Valerie , Pigeyre Marie
Published: June 2024

Background

Educational programs incorporating physical activity (PA) sessions and nutritional workshops have demonstrated potential benefits for overweight and obese pregnant women. However, participation in such programs remains challenging. This prospective study aimed to investigate the factors influencing participation and regular attendance, while examining changes in health behaviors, along with obstetric and neonatal outcomes.

Methods

Pregnant women with at 12–22 weeks’ gestation a BMI ≥ 25 kg/m2 were invited to join an educational program combining three nutritional workshops conducted in groups and 12 weekly PA sessions. They self-selected their participation into the program. Regardless of program uptake and regularity of attendance, the women’s PA levels, eating behaviors, and affectivity were assessed using validated questionnaires at 20–24 weeks, 32–34 weeks, and postpartum. A multivariable logistic regression model was used to determine the factors influencing participation.

Results

Of the 187 women enrolled in the study, 61.5% agreed to participate in the program. Of these, only 45% attended six or more sessions (regardless of the nature of sessions, i.e. nutritional workshops and/or PA sessions), while only 8.7% attended six or more PA sessions. Participation was associated with higher rates of problematic eating behaviors and lower PA levels at baseline, while regular attendance was mainly associated with higher household incomes. No significant difference was observed between participants and non-participants in terms of changes in eating behaviors, PA levels, or affectivity. However, at the 32–34 week visit, regular participants displayed a higher change in positive affectivity, but unexpectedly also in cognitive restraint, than non-regular participants, a difference that did not persist at postpartum.

Conclusion

The educational program combining nutrition and PA was shown to be safe. Women facing challenges related to health behavior displayed a willingness to sign up for the program, but tailored interventions addressing their individual challenges are needed to improve attendance. Accordingly, four recommendations are proposed for the design of future interventions.

Trial registration

ClinicalTrials.gov; Identifier: NCT02701426; date of first registration: 08/03/2016.
Association of effective dose to immune cells and vertebral marrow dose with hematologic toxicity during neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma
Authors: Zhang Meng , Li Zhenjiang , Yin Yong
Published: June 2024

Background

To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell carcinoma (ESCC) during neoadjuvant chemoradiotherapy (nCRT).

Methods

The study included 106 ESCC patients treated with nCRT. We collected dosimetric parameters, including vertebral body volumes receiving 10–40 Gy (V10, V20, V30, V40) and EDIC and complete blood counts. Associations of the cell nadir and dosimetric parameters were examined by linear and logistic regression analysis. The receiver operating characteristic (ROC) curves were used to determine the cutoff values for the dosimetric parameters.

Results

During nCRT, the incidence of grade 3–4 lymphopenia, leukopenia, and neutropenia was 76.4%, 37.3%, and 37.3%, respectively. Patients with EDIC ≤ 4.63 Gy plus V10 ≤ 140.3 ml were strongly associated with lower risk of grade 3–4 lymphopenia (OR, 0.050; P < 0.001), and patients with EDIC ≤ 4.53 Gy plus V10 ≤ 100.9 ml were strongly associated with lower risk of grade 3–4 leukopenia (OR, 0.177; P = 0.011), and patients with EDIC ≤ 5.79 Gy were strongly associated with lower risk of grade 3–4 neutropenia (OR, 0.401; P = 0.031). Kaplan-Meier analysis showed that there was a significant difference among all groups for grade 3–4 lymphopenia, leukopenia, and neutropenia (P < 0.05).

Conclusion

The dose of vertebral bone marrow irradiation and EDIC were significantly correlated with grade 3–4 leukopenia and lymphopenia, and EDIC was significantly correlated with grade 3–4 neutropenia. Reducing vertebral bone marrow irradiation and EDIC effectively reduce the incidence of HT.
Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies
Authors: Wang Minxi , Lu Jiali , Dong Jiyue
Published: June 2024

Background

The purpose of this review was to examine if dipeptidyl peptidase-4 inhibitor (DPP4i) use affects the risk of diabetic retinopathy (DR).

Methods

Cohort studies published up to 20th July 2023 in the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched. The adjusted effect size was pooled to calculate the odds ratio (OR).

Results

Seven studies were included. Meta-analysis showed that the use of DPP4i was not associated with any significant change in the risk of DR (OR: 0.86 95% CI: 0.70, 1.06 I2 = 78%). The pooled analysis also found that DPP4i use was not associated with any significant risk of progression of DR (OR: 0.87 95% CI: 0.47, 1.59 I2 = 86%). The results did not change during sensitivity analysis.

Conclusion

Present evidence from a limited number of real-world studies shows that DPP4i may not affect the incidence and progression of DR. There is a need for further studies from different countries using accurate definitions of DR and its progression to validate the current results.
Decrease in pelvic incidence after adult spinal deformity surgery is a predictive factor for progression of hip joint osteoarthritis
Authors: Tomizawa Kazuo , Inami Satoshi , Moridaira Hiroshi , Ueda Haruki , Sekimoto Iwao , Kanto Tomoya , Taneichi Hiroshi
Published: June 2024

Background

This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment.

Methods

This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint. Spinopelvic alignment parameters were measured preoperatively and 1-month postoperatively and the changes (Δ) during this period were calculated. Patients were followed-up for ≥ 5 years and factors associated with KL grade progression at 5-years postoperatively were determined by logistic regression analysis.

Results

In the analysis with all cases, KL grade progressed in 23 joints. Logistic regression analysis revealed age (OR: 1.098, 95% CI: 1.007–1.198, p = 0.019), ARO (OR: 1.176, 95% CI: 1.01–1.37, p = 0.026), and Δ PI (OR: 0.791, 95% CI: 0.688–0.997, p < 0.001) as parameters significantly associated with KL grade progression. On the other hand, in the analysis limited to 185 cases with 1-month postoperative KL grade of 0, KL grade progressed in 13 joints. Logistic regression analysis revealed PI-LL (OR: 1.058, 95% CI: 1.001–1.117, p = 0.04), ΔPI (OR: 0.785, 95% CI: 0.649–0.951, p < 0.001), and ΔCobb (OR: 1.127, 95% CI: 1.012–1.253, p = 0.009) as parameters significantly associated with progression.

Conclusions

Both the overall and limited analyzes of this study identified preoperative to postoperative change in PI as parameters affecting the hip osteoarthritis progression after spinal fusion surgery. Decrease in PI might represent preexisting sacroiliac joint laxity. Patients with this risk factor should be carefully followed for possible hip osteoarthritis progression.
Knowledge and practices of Iranian students (13–16 age) regarding the use of fluoride toothpaste
Authors: Hashemipour Maryam Alsadat , Zeyghami Zahra , Rajaee Halle
Published: June 2024

Introduction

Fluoride is the main factor in reducing the prevalence of caries worldwide. However, there is insufficient knowledge about whether people in different age groups are aware of the benefits of fluoride toothpaste, as well as about people’s daily oral care habits and whether they use fluoride. The purpose of this research is to investigate the knowledge and performance of Iranian students regarding the use of toothpaste containing fluoride.

Method

This study was conducted on the first- and second-year high school students of Kerman city. Questionnaires containing personal questions, general questions, and questions related to students’ knowledge and performance regarding the use of fluoride toothpaste were provided to them and then they were asked to complete and submit it. The results obtained from the survey were analyzed by T-test, Mann-Whitney test, and Chi-Square test in SPSS Version 24. The significance level in data analysis was P < 0.05.

Results

In this research, 681 forms including 252 boys and 429 girls were examined. The average age of the participants was 14.1 ± 0.4. 91.2% declared that they use toothpaste and 77.8% of them used toothpaste containing fluoride. 521 people stated that the price of toothpaste is important in using the type of toothpaste. 621 people used regular toothbrush and 609 people evaluated their oral health as good. 621 of the participants stated that toothpaste makes the mouth healthy. The average knowledge score was 16.7 ± 2.1 out of 24, which indicates the average knowledge of students in this field.

Conclusion

This study showed that students’ knowledge and performance about using fluoride-containing toothpaste is average. There was no significant relationship between performance and knowledge with age and gender. There was also a positive correlation between knowledge and performance indicating that increasing knowledge leads to an increase in behavioral changes. Also, there was a positive correlation between knowledge and performance, and a correlation coefficient of 0.731 was obtained between knowledge and performance. It shows that increasing knowledge leads to increasing behavioral changes.
Novel antimicrobial applications of copper oxide nanoparticles after combination with tissue conditioner used in complete prostheses
Authors: Nikanjam Saeed , Yeganegi Aria , Alikhani Mohammad-Yousef , Farmany Abbas , Ghiasian Seyed Amir , Hasanzade Roghayeh
Published: June 2024

Background

Tissue conditioners are used for treating and improving the tissues supporting complete dentures. On the other hand, recent advances in nanotechnology have revolutionized various fields of science, including dentistry. The present study aimed to investigate novel antimicrobial applications of copper oxide nanoparticle-based tissue conditioner used in complete prostheses.

Methods

The present experimental study included 126 tissue conditioner samples with different concentrations of copper oxide nanoparticles (20%, 10%, 5%, 2.5%, 1.25%, 0.625%, and 0% w/w). The samples were incubated with Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans in 24-well plates for 24 h. Then, samples from the wells were re-incubated for 24 h, and the microorganisms were counted.

Results

The culture media containing E. faecalis and P. aeruginosa showed significantly different growth between different nanoparticle concentrations following 24 h (P < 0.001), showing a reduction in bacterial growth with increased nanoparticle concentration. Both bacteria did not show any growth at the 20% concentration. However, C. albicans showed significant differences in growth between different nanoparticle concentrations following 48 h (P < 0.001), showing a reduction in growth with increased nanoparticle concentration. Also, the least growth was observed at the 20% concentration.

Conclusions

In conclusion, the CuO nanoparticles were prepared using a green synthesis methon in the suitable sizes. Moreover, the tissue conditioners containing CuO nanoparticles showed acceptable antimicrobial properties against E. faecalis, P. aeruginosa, and C. albicans.
Translating, adapting, and validating the medical student version of the patient care ownership scale for use in Japan
Authors: Fujikawa Hirohisa , Hayashi Mikio , Son Daisuke , Kondo Kayo , Eto Masato
Published: June 2024

Background

Patient care ownership (PCO) among medical students is a growing area in the field of medical education. While PCO has received increasing attention, there are no instruments to assess PCO in the context of Japanese undergraduate medical education. This study aimed to translate, culturally adapt, and validate the PCO Scale – Medical students (PCOS-S) in the Japanese context.

Methods

We collected survey data from fifth- and sixth-grade medical students from five different universities varying in location and type. Structural validity, convergent validity, and internal consistency reliability were examined.

Results

Data from 122 respondents were analyzed. Factor analysis of the Japanese PCOS-S revealed three factors with Cronbach’s alpha values exceeding the satisfactory criterion (0.70). A positive correlation was observed between the total Japanese PCOS-S scores and the global rating scores for the clinical department as a learning environment (Pearson’s correlation coefficient = 0.61).

Conclusions

We conducted the translation of the PCOS-S into Japanese and assessed its psychometric properties. The Japanese version has good reliability and validity. This instrument has potential value in assessing the development of medical students’ PCO.
Exploring the safety reporting culture among healthcare practitioners in Saudi hospitals: a comprehensive 2022 national study
Authors: Alkahf Dyma , Alonazi Wadi
Published: June 2024

Background

With the rise in medical errors, establishing a strong safety culture and an effective incident reporting system is crucial. As part of the Saudi National Health Transformation Vision of 2030, multiple projects have been initiated to periodically assess healthcare quality measures and ensure a commitment to continuous improvement. Among these is the Hospital Survey on Patient Safety Culture National Project (HSPSC), conducted regularly by the Saudi Patient Safety Center (SPSC). However, comprehensive tools for assessing reporting culture are lacking. Addressing this gap can enhance reporting, efficiency, and health safety.

Objective

This paper aims to investigate the reporting practices among healthcare professionals (HCPs) in Saudi Arabian hospitals and examine the relationship between reporting culture domains and other variables such as hospital bed capabilities and HCPs’ work positions.

Methods

The study focuses on measuring the reporting culture-related items measures and employs secondary data analysis using information from the Hospital Survey on Patient Safety Culture conducted by the Saudi Center for Patient Safety in 2022, encompassing hospitals throughout Saudi Arabia. Data incorporated seven items in total: four items related to the Response to Error Domain, two related to the Reporting Patient Safety Events Domain, and one associated with the number of events reported in the past 12 months.

Results

The sample for the analyzed data included 145,657 HCPs from 392 hospitals. The results showed that the average positive response rates for reporting culture-related items were between 50% and 70%. In addition, the research indicated that favorable response rates were relatively higher among managerial and quality/patient safety/risk management staff. In contrast, almost half had not reported any events in the preceding year, and a quarter reported only 1 or 2 events. Pearson correlation analysis demonstrates a strong negative correlation between bed capacity and reporting safety events, response to error, and number of events reported (r = -0.935, -0.920, and − 0.911, respectively; p < 0.05), while a strong positive correlation is observed between reporting safety events and response to error (r = 0.980; p < 0.01).

Conclusions

Almost 75% of the HCPs reported fewer safety events over the last 12 months, indicating an unexpectedly minimal recorded occurrence variance ranging from 0 to 2 incidents.
Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial
Authors: Fujiki Shinya , Iijima Kenichi , Nakagawa Yoshihisa , Takahashi Kazuyoshi , Okabe Masaaki , Kusano Kengo , Owada Shingen , Kondo Yusuke , Tsujita Kenichi , Shimizu Wataru , Tomita Hirofumi , Watanabe Masaya , Shoda Morio , Watanabe Masafumi , Tokano Takashi , Murohara Toyoaki , Kaneshiro Takashi , Kato Takeshi , Hayashi Hidemori , Maemura Koji , Niwano Shinichi , Umemoto Tomio , Yoshida Hisako , Ota Keiko , Tanaka Takahiro , Kitamura Nobutaka , Node Koichi , Minamino Tohru ,   for the EMPA ICD investigators
Published: June 2024

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes.

Methods

A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values.

Results

In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was − 1.07 (95% confidence interval [CI] − 1.29 to − 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight.

Conclusions

In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo.

Trial registration jRCTs031180120.
A call from 40 public health scientists for an end to the continuing humanitarian and environmental catastrophe in Gaza
Authors: London Leslie , Watterson Andrew , Mergler Donna , Albin Maria , Andrade-Rivas Federico , Ciaula Agostino Di , Comba Pietro , Giannasi Fernanda , Habib Rima R , Hay Alastair , Hoppin Jane , Infante Peter , Jeebhay Mohamed , Kelsey Karl , Kim Rokho , Lemen Richard , Lipscomb Hester , Lynge Elsebeth , Magnani Corrado , Monforton Celeste , Nemery Benoit , Ngowi Vera , Nowak Dennis , Nuwayhid Iman , Oliver Christine , Ozonoff David , Paek Domyung , Petrosyan Varduhi , Portier Christopher J , Ritz Beate , Rosenstock Linda , Ruff Kathleen , Sly Peter , Soffritti Morando , Soskolne Colin L. , Suk William , Terracini Benedetto , Vainio Harri Uolevi , Vineis Paolo , White Roberta
Published: June 2024

An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations.