bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol
Authors: Crichton Alison , Harris Katrina , McGree James M , Nikles Jane , Anderson Peter J , Williams Katrina
Published: April 2024

Introduction

Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%–94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD.

Methods and analysis

A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.

Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child’s treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability.

Ethics and dissemination

The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).

Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials.

Trial registration number

NCT04968522.
Effect of metacognitive therapy on depression in patients with chronic disease: a protocol for a systematic review and meta-analysis
Authors: Zhang Zirui , Wang Peng , Gu Jinjin , Zhang Qiang , Sun Changqing , Wang Panpan
Published: April 2024

Background

Chronic diseases have a high prevalence worldwide, and patients with chronic diseases often suffer from depression, leading to a poor prognosis and a low quality of life. Metacognitive therapy is a transdiagnostic psychotherapy intervention focused on thinking patterns, with the advantages of reliable implementation effect, short intervention period and low cost. It can help patients change negative metacognition, alleviate depression symptoms, and has a higher implementation value compared with other cognitive interventions. Therefore, metacognitive therapy may be an effective way to improve the mental health of patients with chronic diseases.

Methods and analysis

CNKI, Wanfang Database, VIP Database for Chinese Technical Periodicals, Sinomed, PubMed, SCOPUS, Embase, The Cochrane Library, Web of Science and PsycINFO will be used to select the eligible studies. As a supplement, websites (eg, the Chinese Clinical Registry, ClinicalTrials.gov) will be searched and grey literature will be included. The heterogeneity and methodological quality of the eligible studies will be independently screened and extracted by two experienced reviewers. All the data synthesis and analysis (drawing forest plots, subgroup analysis and sensitive analysis) will be conducted using RevMan 5.4.1.

Ethics and dissemination

This article is a literature review that does not include patients’ identifiable information. Therefore, ethical approval is not required in this protocol. The findings of this systematic review and meta-analysis will be published in a peer-reviewed journal as well as presentations at relevant conferences.

PROSPERO registration number

CRD42023411105.
Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings
Authors: Rockwell Michelle S , Oyese Emma G , Singh Eshika , Vinson Matthew , Yim Isaiah , Turner Jamie K , Epling John W
Published: April 2024

Objectives

Potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.

Design

Scoping review.

Data sources

PubMed, CINAHL, Embase, Cochrane Central and Google Scholar (1 January 2000 to 31 May 2022).

Study selection

Studies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilisation in healthcare settings.

Data extraction

Using Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilisation.

Results

From 7818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the USA (35.3%), with randomised controlled trial as the most common design (55.9%). Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%) but were rarely (14.9%) guided by an implementation model, framework or theory. Academic detailing, clinical decision support or electronic medical record interventions, performance reports and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients’ age (55.8%), history of gastrointestinal disorders (47.1%), or history of kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter (OTC) NSAIDs in addition to prescription. The majority of studies (76.2%) reported a reduction in the utilisation of potentially harmful NSAIDs. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation.

Conclusion

Many varied interventions to de-implement potentially harmful NSAIDs have been applied in healthcare settings worldwide. Based on these findings and identified knowledge gaps, further efforts to comprehensively evaluate the effectiveness of interventions and the combination of intervention characteristics associated with effective de-implementation are needed. In addition, future work should be guided by de-implementation theory, focus on OTC NSAIDs and incorporate patient-focused strategies and outcomes, including the evaluation of unintended consequences of the intervention.
Cost of SARS-CoV-2 self-test distribution programmes by different modalities: a micro-costing study in five countries (Brazil, Georgia, Malaysia, Ethiopia and the Philippines)
Authors: Hansen Megan A , Lekodeba Nkgomeleng A , Chevalier Joshua M , Ockhuisen Tom , del Rey-Puech Paula , Marban-Castro Elena , Martínez-Pérez Guillermo Zohar , Shilton Sonjelle , Radzi Abu Hassan Muhammad , Getia Vladimir , Weinert-Mizuschima Catiuscia , Tenorio Bezerra Maria Isabelle , Chala Lensa , Leong Robert , Peregino Remilekun , Keller Sara , Spruijt Ineke , Johnson Cheryl C , Girdwood Sarah J , Nichols Brooke E
Published: April 2024

Objective

Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities.

Design

We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction).

Setting

We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings—namely, workplace and healthcare facilities.

Results

Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04–3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58–87% for countries with off-site self-testing (outside the workplace, for example, home) and 15–50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29–35%) versus off-site self-testing (7–27%).

Conclusions

Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.
Barriers and facilitators to using ophthalmic clinical health services following school vision screening: a mixed-methods study
Authors: Lyu Pingping , Shi Jiaojiao , Hu Jingwen , Wang Jingjing , He Xiangui , Shi Huijing
Published: April 2024

Objective

To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening.

Methods

This study employed a sequential explanatory mixed methods design, underpinned by Andersen’s Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders—comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings.

Results

The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).

Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence.

Conclusion

The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.
Ensuring safe and equitable discharge: a quality improvement initiative for individuals with hypertensive disorders of pregnancy
Authors: Zacherl Kathleen M. , Sterrett Emily Carper , Hughes Brenna L. , Whelan Karley M , Tyler-Walker James , Bauer Samuel T , Talley Heather C , Havrilesky Laura J
Published: April 2024

Objective

To improve timely and equitable access to postpartum blood pressure (BP) monitoring in individuals with hypertensive disorders of pregnancy (HDP).

Methods

A quality improvement initiative was implemented at a large academic medical centre in the USA for postpartum individuals with HDP. The primary aim was to increase completed BP checks within 7 days of hospital discharge from 40% to 70% in people with HDP in 6 months. Secondary aims included improving rates of scheduled visits, completed visits within 3 days for severe HDP and unattended visits. The balancing measure was readmission rate. Statistical process control charts were used, and data were stratified by race and ethnicity. Direct feedback from birthing individuals was obtained through phone interviews with a focus on black birthing people after a racial disparity was noted in unattended visits.

Results

Statistically significant improvements were noted across all measures. Completed and scheduled visits within 7 days of discharge improved from 40% to 76% and 61% to 90%, respectively. Completed visits within 3 days for individuals with severe HDP improved from 9% to 49%. The unattended visit rate was 26% at baseline with non-Hispanic black individuals 2.3 times more likely to experience an unattended visit than non-Hispanic white counterparts. The unattended visit rate decreased to 15% overall with an elimination of disparity. A need for BP devices at discharge and enhanced education for black individuals was identified through patient feedback.

Conclusion

Timely follow-up of postpartum individuals with HDP is challenging and requires modification to our care delivery. A hospital-level quality improvement initiative using birthing individual and frontline feedback is illustrated to improve equitable, person-centred care.
Post-trial access to implantable neural devices: an exploratory international survey
Authors: Higgins Nathan , Gardner John , Wexler Anna , Kellmeyer Philipp , O'Brien Kerry , Carter Adrian
Published: April 2024

Objectives

Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants’ post-trial access to the device and ongoing clinical care. This exploratory study examines common practices in the planning and coordination of post-trial access to neurosurgical devices. We also explore the perspectives of trial investigators on the barriers to post-trial access and ongoing care, as well as ethical questions related to the responsibilities of key stakeholder groups.

Design, setting, and participants

Trial investigators (n=66) completed a survey on post-trial access in the most recent investigational trial of a surgically implanted neural device they had conducted. Survey respondents predominantly specialized in neurosurgery, neurology and psychiatry, with a mean of 14.8 years of experience working with implantable neural devices.

Main outcome measures

Outcomes of interest included rates of device explantation during or at the conclusion of the trial (pre-follow-up) and whether plans for post-trial access were described in the study protocol. Outcomes also included investigators’ greatest ‘barrier’ and ‘facilitator’ to providing research participants with post-trial access to functional implants and perspectives on current arrangements for the sharing of post-trial responsibilities among key stakeholders.

Results

Trial investigators reported either ‘all’ (64%) or ‘most’ (33%) trial participants had remained implanted after the end of the trial, with ‘infection’ and ‘non-response’ the most common reasons for explantation. When asked to describe the main barriers to facilitating post-trial access, investigators described limited funding, scarcity of expertise and specialist clinical infrastructure and difficulties maintaining stakeholder relationships. Notwithstanding these barriers, investigators overwhelmingly (95%) agreed there is an ethical obligation to provide post-trial access when participants individually benefit during the trial.

Conclusions

On occasions when devices were explanted during or at the end of the trial, this was done out of concern for the safety and well-being of participants. Further research into common practices in the post-trial phase is needed and essential to ethical and pragmatic discussions regarding stakeholder responsibilities.
Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study
Authors: Cuthbert Joseph James , Soyiri Ireneous , Lomax Stephanie Jayne , Turgoose John , Fuat Ahmet , Cohen Judith , Clark Andrew L
Published: April 2024

Background

Loop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics without a diagnosis of HF is unknown.

Methods

This was a propensity-matched cohort study using data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office of National Statistics in the UK. Patients prescribed a loop diuretic without a diagnosis of HF (loop diuretic group) between 1 January 2010 and 31 December 2015 were compared with patients with HF (HF group)—analysis A, and patients with risk factors for HF (either ischaemic heart disease, or diabetesandhypertension—at-risk group)—analysis B. The primary endpoint was an HF event (a composite of presentation with HF symptoms, HF hospitalisation, HF diagnosis (analysis B only) and all-cause mortality).

Results

From a total population of 180 384 patients (78 968 in the loop diuretic group, 28 177 in the HF group and 73 239 in the at-risk group), there were 59 694 patients, 22 352 patients and 57 219 patients in the loop diuretic, HF and at-risk groups, respectively, after exclusion criteria were applied. After propensity matching for age, sex and comorbidities, patients in the loop diuretic group had a similar rate of HF events as those in the HF group (71.9% vs 72.1%; HR=0.92 (95% CI 0.90 to 0.94); p<0.001), and twice as those in the at-risk group (59.2% vs 35.7%; HR=2.04 (95% CI 2.00 to 2.08); p<0.001).

Conclusions

Patients prescribed a loop diuretic without a recorded diagnosis of HF experience HF events at a rate comparable with that of patientswitha recorded diagnosis of HF; many of these patients may have undiagnosed HF.
Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer
Authors: Razmara Aryana M , Farley Lauren E , Harris Rayna M , Judge Sean J , Lammers Marshall , Iranpur Khurshid R , Johnson Eric G , Dunai Cordelia , Murphy William J , Brown C Titus , Rebhun Robert B , Kent Michael S , Canter Robert J
Published: April 2024

Background

Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product.

Methods

Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3’-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach.

Results

Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment.

Conclusions

Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.
Higher mortality risk from gynaecological neoplasms and non-Hodgkin’s lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry
Authors: Moreno-Torres Víctor , Martínez-Urbistondo María , Vázquez-Comendador José , Mateos Seirul-lo María , Castejón Raquel , Huerta Ana , Durán-del Campo Pedro , Tutor Pablo , Mellor-Pita Susana
Published: April 2024

Objective

To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE.

Methods

Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed.

Results

During 2016–2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin’s lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133).

Conclusions

Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin’s lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.
Updates on the determination of $$\vert V_{cb} \vert ,$$ $$R(D^{*})$$ and $$\vert V_{ub} \vert /\vert V_{cb} \vert $$
Authors: Martinelli G. , Simula S. , Vittorio L.
Published: April 2024

We present an updated determination of the values of $$\vert V_{cb} \vert ,$$

|

V

cb

|
,

$$R(D^*)$$

R
(

D
∗

)

and $$\vert V_{ub} \vert /\vert V_{cb} \vert $$

|

V

ub

|
/
|

V

cb

|

based on the new data on semileptonic $$B \rightarrow D^* \ell \nu _\ell $$

B
→

D
∗

ℓ

ν
ℓ

decays by the Belle and Belle-II Collaborations and on the recent theoretical progress in the calculation of the form factors relevant for semileptonic $$B \rightarrow D^* \ell \nu _\ell $$

B
→

D
∗

ℓ

ν
ℓ

and $$B_s \rightarrow K \ell \nu _\ell $$

B
s

→
K
ℓ

ν
ℓ

decays. In particular we present results derived by applying either the Dispersive Matrix (DM) method of Di Carlo et al. (Phys Rev D 104:054502, 2021), Martinelli et al. (Phys Rev D 104:094512, 2021), Martinelli et al. (Phys Rev D 105:034503, 2022), Martinelli et al. (Eur Phys J C 82:1083, 2022), Martinelli et al. (JHEP 08:022, 2022) and Martinelli et al. (Phys Rev D 106:093002, 2022) or the more standard Boyd–Grinstein–Lebed (BGL) (Boyd et al. in Phys Rev D 56:6895, 1997) approach to the most recent values of the form factors determined in lattice QCD. Using all the available lattice results for the form factors from the DM method we get the theoretical value $$R^{\textrm{th}}(D^*) = 0.262 \pm 0.009$$

R
th

(

D
∗

)

=
0.262
±
0.009

and we extract from a bin-per-bin analysis of the experimental data the value $$\vert V_{cb} \vert = (39.92 \pm 0.64) \cdot 10^{-3}.$$

|

V

cb

|
=

(
39.92
±
0.64
)

·

10

-
3

.

Our result for $$R(D^*)$$

R
(

D
∗

)

is consistent with the latest experimental world average $$R^{\textrm{exp}}(D^*) = 0.284 \pm 0.012$$

R
exp

(

D
∗

)

=
0.284
±
0.012

(HFLAV Collaboration in Preliminary average of R(D) and $$R(D^*)$$

R
(

D
∗

)

as for Summer 2023. See https://hflav-eos.web.cern.ch/hflav-eos/semi/summer23/html/RDsDsstar/RDRDs.html) at the $$\simeq 1.5\,\sigma $$

≃
1.5

σ

level. Our value for $$\vert V_{cb} \vert $$

|

V

cb

|

is compatible with the latest inclusive determinations $$\vert V_{cb} \vert ^{\textrm{incl}} = (41.97 \pm 0.48) \cdot 10^{-3}$$

|

V

cb

|

incl

=

(
41.97
±
0.48
)

·

10

-
3

(Finauri and Gambino in The $$q^2$$

q
2

moments in inclusive semileptonic B decays. arXiv:2310.20324) and $$\vert V_{cb} \vert ^{\textrm{incl}} = (41.69\pm 0.63) \cdot 10^{-3}$$

|

V

cb

|

incl

=

(
41.69
±
0.63
)

·

10

-
3

(Bernlochner et al. in JHEP 10:068, 2022) within $$\simeq 2.6$$

≃
2.6

and $$\simeq 2.0$$

≃
2.0

standard deviations, respectively. From a reappraisal of the calculations of $$\vert V_{ub} \vert / \vert V_{cb} \vert ,$$

|

V

ub

|
/
|

V

cb

|
,

we also obtain $$\vert V_{ub} \vert / \vert V_{cb} \vert = 0.087\pm 0.009$$

|

V

ub

|
/
|

V

cb

|
=
0.087
±
0.009

in good agreement with the result $$\vert V_{ub} \vert / \vert V_{cb} \vert = 0.0844\pm 0.0056$$

|

V

ub

|
/
|

V

cb

|
=
0.0844
±
0.0056

from the latest FLAG review (Flavour Lattice Averaging Group (FLAG) Collaboration in Phys J C 82:869, 2022).
OPTIMIZATION OF LASER PARAMETERS USING NSGA-II FOR THE GENERATION OF BIOINSPIRED SURFACE
Authors: JAGANNATHAN PREETHA , TAMANG SANTOSH KUMAR , THANIGAIVELAN R. , JAGADEESHA T.
Published: April 2024

The necessity for innovative biomaterials has been growing recently due to the rising cost of materials for intricate biomedical equipment. An important tactic to improve critical attributes like hemocompatibility, osseointegration potential, corrosion resistance, and antibacterial capabilities is surface modification. In this paper, an investigation has been made in the field of laser surface modification and the complex interactions between laser parameters and output performance metrics, such as contact angle and surface roughness. Surface modification by laser has been successful and, in this research, the laser parameters such as laser energy (Watts), standoff distance(mm), and frequency (kHz) along with dimple distance on the surface ([Formula: see text]m) were considered on the output performance namely surface roughness in “[Formula: see text]m” and contact angle in “degree”. The experiment has been carried out using the L16 orthogonal array to interpret the complex correlations between these factors and the resulting surface features. Non-dominated sorting genetic algorithm II (NSGA-II) has successfully navigated the complex parameter space and found the optimal combinations that yield the intended outcomes. The results show how important dimple distance and laser frequency are in creating hydrophobic surfaces, as well as how much of an impact they have on surface properties. It has been discovered that higher frequencies and longer standoff distances specifically reduce surface roughness, which is a crucial component in ensuring enhanced biomaterial performance. The result shows that the dimple distance and frequency of the laser have a significant effect on the development of hydrophobic surfaces. Moreover, high frequency and more standoff distance reduce the surface roughness. The predicted combination of laser parameters as per the NSGA-II is 102.91[Formula: see text][Formula: see text]m, 33.35[Formula: see text]W, 223.12[Formula: see text]mm, 50.01[Formula: see text]kHz, and gives a surface roughness of 0.86[Formula: see text][Formula: see text]m and contact angle of 158.83∘. In essence, this study not only sheds light on the intricate dynamics governing laser-based surface modification but also paves the way for the design and development of advanced biomaterials with tailored surface properties, poised to revolutionize biomedical applications.
Faster Counting and Sampling Algorithms using Colorful Decision Oracle
Authors: Bhattacharya Anup , Bishnu Arijit , Ghosh Arijit , Mishra Gopinath
Published: April 2024

In this work, we consider
d
-
Hyperedge Estimation
and
d
-
Hyperedge Sample
problems that deal with estimation and uniform sampling of hyperedges in a hypergraph ℋ(
U
(ℋ), ℱ(ℋ) in the query complexity framework, where
U
(ℋ) denotes the set of vertices and ℱ(ℋ) denotes the set of hyperedges. The oracle access to the hypergraph is called
Colorful Independence Oracle
(
CID
), which takes
d
(non-empty) pairwise disjoint subsets of vertices
A
1
,...,

A
d

⊆
U
(ℋ) as input and answers whether there exists a hyperedge in ℋ having exactly one vertex in each

A
i

for all
i
∈ {1, 2, ...,
d
}. Apart from the fact that
d
-
Hyperedge Estimation
and
d
-
Hyperedge Sample
problems with
CID
oracle access seem to be nice combinatorial problems, Dell et al. [SODA’20 & SICOMP’22] established that
decision
vs.
counting
complexities of a number of combinatorial optimization problems can be abstracted out as
d
-
Hyperedge Estimation
problem with a
CID
oracle access.

The main technical contribution of this article is an algorithm that estimates
m
= |ℱ(ℋ)| with

\(\widehat{m}\)

such that

\(\begin{equation*}
\frac{1}{C_{d}\log ^{d-1} n} \;\le \; \frac{\widehat{m}}{m} \;\le \; C_{d} \log ^{d-1} n
\end{equation*}\)

by using at most

C
d

log

d
+2

n
CID
queries, where
n
denotes the number of vertices in the hypergraph ℋ and

C
d

is a constant that depends only on
d
. Our result, when coupled with the framework proposed by Dell et al. (SODA’20 & SICOMP’22), leads to implies improved bounds for (1 ± ε)-approximation (where ε ∈ (0,1)) for the following fundamental problems:

Edge Estimation

using the
Bipartite Independent Set
(
BIS
) query. We improve the bound obtained by Beame et al. (ITCS’18 & TALG’20).

Triangle Estimation

using the
Tripartite Independent Set
(
TIS
) query. Currently, Dell et al.’s result gives the best bound for the case of triangle estimation in general graphs (SODA’20 & SICOMP’22). The previous best bound for the case of graphs with low
co-degree
(co-degree of a graph is the maximum number of triangles incident over any edge of the graph) was due to Bhattacharya et al. (ISAAC’19 & TOCS’21). We improve both of these bounds.

Hyperedge Estimation & Sampling

using
Colorful Independence Oracle
(
CID
). We give an improvement over the bounds obtained by Dell et al. (SODA’20 & SICOMP’22).
Net Loss: An econometric method to measure the impact of Internet shutdowns
Authors: Tagat Anirudh , Phokeer Amreesh , Kreitem Hanna M.
Published: April 2024

The economic costs of Internet shutdowns are far-reaching and widespread and span beyond the simple disruption to communication networks that are reliant on access to the Internet. Existing work on the impacts of the Internet shutdowns does not extensively exploit the fact that they can have adverse effects on the local economy in terms of output, employment, and investments. There is a lack of rigorous economic analysis of the impacts of shutdowns that can be more broadly applied to specific regions that account for variations in the intensity (or type) of shutdowns, as well as go beyond providing broad Gross Domestic Product (GDP) cost estimates, which may be misleading. This article aims to bridge this gap by providing an econometric approach to estimate the impact of Internet shutdowns on GDP, employment, and foreign direct investment using panel data on 92 countries. We show that a point increase in the likelihood of an Internet shutdown was statistically significantly associated with a 15.6 percentage point reduction in the GDP per capita on average and every additional day of an Internet shutdown costs $86.58 per person on average.
An adaptive dual graph convolution fusion network for aspect-based sentiment analysis
Authors: Wang Chunmei , Luo Yuan , Meng Chunli , Yuan Feiniu
Published: April 2024

Aspect-based Sentiment Analysis (ABSA), also known as fine-grained sentiment analysis, aims to predict the sentiment polarity of specific aspect words in the sentence. Some studies have explored the semantic correlation between words in sentences through attention-based methods. Other studies have learned syntactic knowledge by using graph convolution networks to introduce dependency relations. These methods have achieved satisfactory results in the ABSA tasks. However, due to the complexity of language, effectively capturing semantic and syntactic knowledge remains a challenging research question. Therefore, we propose an Adaptive Dual Graph Convolution Fusion Network (AD-GCFN) for aspect-based sentiment analysis. This model uses two graph convolution networks: one for the semantic layer to learn semantic correlations by an attention mechanism, and the other for the syntactic layer to learn syntactic structure by dependency parsing. To reduce the noise caused by the attention mechanism, we designed a module that dynamically updates the graph structure information for adaptively aggregating node information. To effectively fuse semantic and syntactic information, we propose a cross-fusion module that uses the double random similarity matrix to obtain the syntactic features in the semantic space and the semantic features in the syntactic space, respectively. Additionally, we employ two regularizers to further improve the ability to capture semantic correlations. The orthogonal regularizer encourages the semantic layer to learn word semantics without overlap, while the differential regularizer encourages the semantic and syntactic layers to learn different parts. Finally, the experimental results on three benchmark datasets show that the AD-GCFN model is superior to the contrast models in terms of accuracy and macro-F1.
Highly Efficient Non-Enzymatic Electrochemical Glucose Biosensor Based on Copper Metal Organic Framework Coated on Graphite Sheet
Authors: Kumari Deepa , Prajapati Megha , Ravi Kant Chhaya
Published: April 2024

Detection of glucose is highly informative, creating a constant demand for fabricating high-precision glucose biosensors. Metal–organic frameworks, a family of porous materials renowned for their tunability, can be an excellent choice for developing such sensors. We have developed a highly-sensitive, non-enzymatic sensor for electrochemical detection of glucose fabricated using Copper Metal–Organic Framework (Cu MOF), synthesized by a simple, room-temperature stirring method using Benzene-1,3,5-tricarboxylic acid (BTC) as ligand and Copper nitrate trihydrate as precursor. The synthesized nanostructure was characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray analytical techniques. Powder X-ray diffraction study and thermogravimetric analysis were also done. Further, Brunnauer-Emmett-Teller analysis revealed the porous nature of Cu MOF. The materials exhibited strong electro-catalytic activity for glucose oxidation as revealed from cyclic voltammetry and chronoamperometric studies done under alkaline pH conditions. The Cu MOF deposited on a conducting graphite sheet electrode displayed a significantly low detection limit of 0.019 mM through a broad detection range (1–15 mM) and a strong sensitivity of 229.4 μAmM−1 cm2. Overall, the Cu MOF/GS exhibits exceptional stability, short response time (less than 1 s), and good repeatability and reproducibility, making it a promising future material for non-enzymatic glucose detection.
Investigation of Magnetocaloric Effect and Critical Field Analysis of Nd0.7−xLaxSr0.3MnO3 (x = 0.0−0.3) Manganites
Authors: Vadnala Sudharshan , Rao T. D. , Pal Munendra , Asthana Saket
Published: April 2024

This research explored the temperature dependence magnetization, magnetocaloric effect, and critical field analysis of Nd0.7−xLaxSr0.3MnO3 (x = 0.0, 0.1, 0.2 and 0.3) manganites samples synthesized through solid state reaction route. The substitution of La3+ at Nd3+ site enhances the A-site average ionic radius (

r

A

) from 1.321 Å (for x = 0.0) to 1.348 Å (for x = 0.3). An increase in

r

A

reduced the internal chemical pressure inside the lattice such that the Mn–O–Mn bond angle approached 180°. In addition, an increase in Mn–O–Mn bond angle supresses the spin-lattice interaction, which consequently reduces the change in maximum magnetic entropy

(
Δ

S

M

max

)

at the magnetic transition temperature. This implies that variation of A-site average ionic radius influences the change in maximum magnetic entropy. The critical behavior of the manganite samples was addressed based on the data of magnetization measurements around the transition temperature TC. Various techniques such as modified Arrott plot, a Kouvel–Fisher method, and critical isotherm analysis were used to measure the values of the ferromagnetic transition temperature TC, as well as the critical exponents of β, γ, and δ. The magnetic order parameter

n

is very well obeyed with scaling relation with change in magnetic entropy.
A comparison of wavelet-based action potential detection from the NeuroAmp and the Iowa Bioengineering Nerve Traffic Analysis system
Authors: Thrall Scott F. , D’Souza Andrew W. , Abrahamson-Durant Brendan , Vianna Lauro C. , Limberg Jacqueline K. , Macefield Vaughan G. , Foster Glen E.
Published: April 2024

The morphology of custom mother wavelets produced across laboratories using the NeuroAmp was highly similar, but distinct from the University of Iowa Bioengineering Nerve Traffic Analysis System. Although the number of action potentials detected was similar between collection systems and mother wavelets, the predictive value differed. Our data suggest action potential analysis using the continuous wavelet transform requires a mother wavelet optimized for the collection system.
The Association between Histidine-Rich Glycoprotein rs10770 Genotype and Recurrent Miscarriage in Iranian Women
Authors: Latifimehr Mahbobeh , Nazari Leila , Rastegari Ali Asghar , Zamani Zahra , Fard-Esfahani Pezhman
Published: April 2024

Purpose. Recurrent miscarriage (RM) is a significant reproductive concern affecting numerous women globally. Genetic factors are believed to play a crucial role in RM, making the histidine-rich glycoprotein (HRG) gene, a topic of interest due to its potential involvement in angiogenesis. This study is aimed at investigating the association between the HRG rs10770 genotype and RM. Method. Blood samples were collected from a total of 200 women at the beginning of the study. Subsequently, a comparative analysis was conducted between the blood samples of 100 women with a history of RM (case group) and the blood samples of another 100 healthy women (control group). HRG rs10770 genotyping was performed through polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP), followed by statistical analysis to evaluate the relationship between HRG rs10770 genotype and RM. Results. The results indicated a significant statistical difference between the C/C genotype (OR=3.32, CI: 1.22-9.04, p=0.01) and the C/T genotype (OR=1.24, CI: 0.67-2.30, p=0.47) in both the case and control groups. Additionally, a significant correlation was observed in the C allelic frequency among RM participants compared to the control group (OR=1.65, CI: 1.06-2.58, p=0.02). Conclusion. The study highlights the importance of HRG rs10770 in understanding RM, shedding light on its implications for reproductive health. Furthermore, it became evident that women carrying the homozygous C/C genotype exhibited increased susceptibility to the risk of RM.
Protein Expression of TLR2, TLR4, and TLR9 on Monocytes in TB, HIV, and TB/HIV
Authors: Tamene Wegene , Wassie Liya , Marconi Vincent C. , Abebe Meseret , Kebede Amha , Sack Ulrich , Howe Rawleigh
Published: April 2024

Toll‐like receptors (TLRs) have a critical role in recognizing pathogenic patterns and initiating immune responses against TB and HIV. Previously, studies described the gene expression of TLRs in patients with TB and HIV. Here, we demonstrated TLRs protein expressions and their association with clinical status and plasma markers in TB, HIV, and TB/HIV coinfection. The phenotyping of TLR2, TLR4, and TLR9 on CD14+ monocytes and their subsets were determined by multicolor flow cytometry. Host plasma biomarkers and microbial indices were measured using Luminex Multiplex assay and standard of care tools, respectively. TLR2 expression significantly enhanced in TB, slightly increased in HIV but slightly reduced in TB/HIV coinfection compared to apparently health controls (HC). On the other hand, TLR4 expression was significantly increased in TB, HIV, and TB/HIV compared to HC. Expression of TLR4 was equally enhanced on classical and intermediate monocytes while higher TLR2 expression on intermediate than classical monocytes. TLR4 had a positive correlation pattern with plasma biomarkers while TLR2 had an inverse correlation pattern. TLR4 is associated with disease severity while TLR2 is with the immune‐competent status of patients. Our findings demonstrated that the pattern of TLR expression is disease as well as monocyte subset specific and distinct factors drive these differences.
Similarity of C1: Operators and the Hyperinvariant Subspace Problem
Authors: Segres Abdelkader , Bachir Ahmed , Ould Ahmed Mahmoud Sid Ahmed
Published: April 2024

In the present paper, we first show that the existence of the solutions of the operator equation S∗XT=X is related to the similarity of operators of class C1., and then we give a sufficient condition for the existence of nontrivial hyperinvariant subspaces. These subspaces are the closure of ranφT for some singular inner functions φ. As an application, we prove that every C10-quasinormal operator and C10-centered operator, under suitable conditions, have nontrivial hyperinvariant subspaces.
Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: April 2024

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens (Ag) and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. In this study, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of Ags and cytosine-guanosine oligodeoxynucleotide (CpG) to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking Ags to eTAT enhanced cytosolic delivery of the Ags. This, in turn, led to improved activation and lymph node–trafficking of Ag-presenting cells and Ag cross-presentation, thus promoting Ag-specific T-cell immune responses. Simple mixing of eTAT-linked Ags and CpG significantly enhanced codelivery of Ags and CpG to the Ag-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity, and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide–based orchestrated codelivery of Ag and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.
Small Extracellular Vesicles Promote Stiffness-mediated Metastasis
Authors: Sneider Alexandra , Liu Ying , Starich Bartholomew , Du Wenxuan , Nair Praful R. , Marar Carolyn , Faqih Najwa , Ciotti Gabrielle E. , Kim Joo Ho , Krishnan Sejal , Ibrahim Salma , Igboko Muna , Locke Alexus , Lewis Daniel M. , Hong Hanna , Karl Michelle N. , Vij Raghav , Russo Gabriella C. , Gómez-de-Mariscal Estibaliz , Habibi Mehran , Muñoz-Barrutia Arrate , Gu Luo , Eisinger-Mathason T.S. Karin , Wirtz Denis
Published: April 2024

Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiologic matrix stiffness affects the quantity and protein cargo of small extracellular vesicles (EV) produced by cancer cells, which in turn aid cancer cell dissemination. Primary patient breast tissue released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4, ITGα6β1, CD44) compared with EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix proteins including collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer-associated fibroblast phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment.

Significance:

Here we show that the quantity, cargo, and function of breast cancer–derived EVs vary with mechanical properties of the extracellular microenvironment.