bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the impact of glucokinase activation on risk of cardiovascular disease: a Mendelian randomisation analysis
Authors: Wang Ke , Shi Mai , Huang Chuiguo , Fan Baoqi , Luk Andrea O. Y. , Kong Alice P. S. , Ma Ronald C. W. , Chan Juliana C. N. , Chow Elaine
Published: September 2022

Background

Glucokinase activators (GKAs) are an emerging class of glucose lowering drugs that activate the glucose-sensing enzyme glucokinase (GK). Pending formal cardiovascular outcome trials, we applied two-sample Mendelian randomisation (MR) to investigate the impact of GK activation on risk of cardiovascular diseases.

Methods

We used independent genetic variants in or around the glucokinase gene meanwhile associated with HbA1c at genome-wide significance (P < 5 × 10−8) in the Meta-Analyses of Glucose and Insulin-related traits Consortium study (N = 146,806; European ancestry) as instrumental variables (IVs) to mimic the effects of GK activation. We assessed the association between genetically proxied GK activation and the risk of coronary artery disease (CAD; 122,733 cases and 424,528 controls), peripheral arterial disease (PAD; 7098 cases and 206,541 controls), stroke (40,585 cases and 406,111 controls) and heart failure (HF; 47,309 cases and 930,014 controls), using genome-wide association study summary statistics of these outcomes in Europeans. We compared the effect estimates of genetically proxied GK activation with estimates of genetically proxied lower HbA1c on the same outcomes. We repeated our MR analyses in East Asians as validation.

Results

Genetically proxied GK activation was associated with reduced risk of CAD (OR 0.38 per 1% lower HbA1c, 95% CI 0.29–0.51, P = 8.77 × 10−11) and HF (OR 0.54 per 1% lower HbA1c, 95% CI 0.41–0.73, P = 3.55 × 10−5). The genetically proxied protective effects of GKA on CAD and HF exceeded those due to non-targeted HbA1c lowering. There was no causal relationship between genetically proxied GK activation and risk of PAD or stroke. The estimates in sensitivity analyses and in East Asians were generally consistent.

Conclusions

GKAs may protect against CAD and HF which needs confirmation by long-term clinical trials.
Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population
Authors: Song Shinjeong , Choi Su‑Yeon , Park Hyo Eun , Han Hae‑Won , Park Sung Hak , Sung Jidong , Jung Hae Ok , Sung Ji Min , Chang Hyuk‑Jae
Published: September 2022

Background

The triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population.

Methods

We enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline.

Results

CAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group.

Conclusion

The TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.
Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer
Authors: Su Pengfei , Jiang Lin , Zhang Yingjing , Yu Tian , Kang Weiming , Liu Yuqin , Yu Jianchun
Published: September 2022

Background

5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated.

Methods

Immunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored.

Results

The high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5.

Conclusion

Interaction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell–cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.
Challenges for drug checking services in Scotland: a qualitative exploration of police perceptions
Authors: Falzon Danilo , Aston Elizabeth V. , Carver Hannah , Masterton Wendy , Wallace Bruce , Sumnall Harry , Measham Fiona , Fletcher Emma , Gittins Rosalind , Priyadarshi Saket , Parkes Tessa
Published: September 2022

Background

The impact of policing practices on the engagement of people who use drugs (PWUD) with harm reduction services is well evidenced. Although the police have traditionally taken an enforcement role in responding to drug use, it is increasingly clear that they can play an important part in multiagency delivery of harm reduction interventions. Despite this, there have been no studies exploring police officer perceptions of drug checking services (DCS), which provide analytical testing of client drug samples alongside harm reduction support and advice.

Methods

Semi-structured interviews were conducted with 10 police officers to explore the policing and legal challenges which could be encountered in the delivery of DCS in Scotland.

Results

Participants expressed general support for DCS and described this support as part of a wider organisational shift towards public health-oriented policing. Participants also discussed different potential approaches to the policing of areas surrounding DCS including: formal limits on police presence around the service and/or stop and search powers in relation to personal possession; the effective decriminalisation of personal possession within a specified boundary around the service; and informal agreements between local divisions and DCS outlining expected policing practices. Any formal limitation on the capacity of police officers to respond to community concerns was viewed as problematic and as having the potential to erode public confidence in policing. Participants also highlighted the potential for frontline officers to utilise discretion in ways which could undermine public health goals. Legislative change, or national strategic guidance from relevant stakeholders, was seen as a means of providing ‘cover’, enabling local divisions to support the operation of drug checking.

Conclusions

Despite a small sample of participants, this study summarises key challenges to be addressed in the implementation and operation of DCS in Scotland, and more widely. The paper concludes with suggested opportunities to develop approaches to policing that can facilitate rather than impede implementation and operation of these services.
The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
Authors: Sternak Marko , Glasnović Anton , Josić Paula , Romić Dominik , Gajović Srećko
Published: September 2022

Background

The spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke.

Aim of the study

To analyze splenectomy as a preclinical intervention in murine models of ischemic stroke.

Methods

Following systematic searches of PubMed, Scopus and Web of Science, a qualitative synthesis of study characteristics was performed, and the effect of splenectomy estimated by a three-level random-effects meta-analysis of infarct volumes and a conventional two-level random-effects meta-analysis of neurological deficit scores.

Results

Database searches identified a total of 14 studies, 13 of which were used for meta-analysis. The ischemic lesion volumes were reduced in splenectomized animals compared to the control groups (difference in standardized mean differences: − 1.42; 95% CI [− 1.98, − 0.85]; 95% PI [− 2.03, − 0.80];I2(2) = 19.04%; 95% CI [0.00%, 65.49%];I2(3) = 47.24%; 95% CI [0.00%, 85.23%]) and neurological deficit scores were improved (− 1.20; 95% CI [− 2.20, − 0.20]; 95% PI [− 4.58, 2.18];I2 = 77.5%; 95% CI [50.0%, 89.9%]). A subgroup analysis for infarct volumes showed that splenectomy performed prior to ischemia achieved a higher reduction of the ischemic lesion than when splenectomy was performed immediately prior or after stroke. Although the overall effect size of splenectomy could be classified as large, there was a significant presence of risks of bias, study heterogeneity, and a potential presence of publication bias.

Conclusion

Despite limitations related to heterogeneity, risks of bias, and potential publication bias, this meta-analysis points to the spleen and its functional cell populations as promising targets for the therapeutic modulation of post-stroke inflammation.
Prolonged mean response time in older adults with cardiovascular risk compared to healthy older adults
Authors: Kominami Kazuyuki , Akino Masatoshi
Published: September 2022

Background

During incremental exercise (Inc-Ex), the mean response time (MRT) of oxygen uptake (V̇O2) represents the time delay before changes in muscle V̇O2 reflect at the mouth level. MRT calculation by linear regression or monoexponential (τ’) fitting of V̇O2 data are known to be highly variable, and a combination of incremental and constant load exercise (CL-Ex) is more reproducible.

Methods

We evaluated MRT in older adults using linear regression and combination methods. We recruited 20 healthy adults (male: 9, 69.4 ± 6.8 years) and 10 cardiovascular risk subjects (male: 8, 73.0 ± 8.8 years). On day 1, they performed Inc-Ex using a 10W/min ramp protocol, for determination of the ventilatory anaerobic threshold (VAT) using the V-slope method. On day 2, they performed Inc-Ex to VAT exercise intensity and CL-Ex for 25min total. The MRT was calculated from the CL-Ex V̇O2 average and the time at equivalent V̇O2 in the Inc-Ex. We also assessed the amount of physical activity using the International Physical Activity Questionnaire short form (IPAQ-SF).

Results

The MRT of healthy participants and those at cardiovascular risk were 49.2 ± 36.3 vs. 83.6 ± 45.4s (p = 0.033). Total physical activity in the IPAQ-SF was inversely correlated with MRT.

Conclusion

The MRT was significantly prolonged in cardiovascular risk participants compared to healthy participants, possibly related to the amount of daily physical activity. Individual MRT may be useful for adjustment of exercise intensity, but this should also be based on daily physical activity and individual condition during exercise.
Mucinous cystic neoplasm of the liver with polypoid nodule prolapsing into the bile duct: a case report and review of literature
Authors: Fukui Yasuhiro , Murata Akihiro , Shimizu Sadatoshi , Sai Kayo , Okada Takuma , Tashima Tetsuzo , Kodai Shintaro , Kanazawa Akishige , Okuno Takahiro
Published: September 2022

Background

Mucinous cystic neoplasm of the liver (MCN-L) is a rare cystic tumor as defined by the 2010 World Health Organization classification. MCN-L usually does not communicate with or grow into the bile duct. Herein, we present a rare case of MCN-L with a polypoid nodule protruding into the bile duct.

Case presentation

A 69-year-old woman was referred to our hospital for elevated serum liver enzyme levels and obstructive jaundice. The patient also complained of abdominal pain in the right hypochondriac region. Abdominal ultrasonography showed a cystic lesion in segment 4 (S4) of the liver. Computed tomography revealed a 4-cm multilocular cystic lesion with a thick wall and multiple septal formations, showing a cyst-in-cyst appearance in S4. Endoscopic retrograde cholangiography showed a contrast defect between the left hepatic duct and the common bile duct, which was suspected to be a nodular lesion in the bile duct. Bile cytology and biopsy of the nodular lesion showed no malignant findings. Based on these findings, the differential diagnosis in this patient included intraductal papillary neoplasm of the bile duct and MCN-L, which had malignant potential. The patient underwent left hemihepatectomy, including caudate lobe excision with bile duct resection and right hepatocholangiojejunostomy. Macroscopic findings showed a 40 × 29 mm multilocular cystic lesion with a polypoid nodule that protruded into the left intrahepatic bile duct. As an ovarian-like stroma was observed in both cystic and polypoid lesions microscopically, the histopathological diagnosis was MCN-L. The postoperative course was uneventful, and the patient was discharged 24 days after surgery. The patient is currently alive without recurrence 22 months after the surgery.

Conclusion

Although MCN-L rarely communicates with the bile duct, it is necessary to consider that MCN-L could grow into the bile duct, occasionally causing obstructive jaundice.
Sudden hemothorax as a rare initial manifestation of bronchiectasis under a direct oral anticoagulant
Authors: Nakayama Hikaru , Uebayashi Asuka , Yagi Shota , Iizuka Shuhei , Otsuki Yoshiro , Nakamura Toru
Published: September 2022

Background

A hemothorax as the initial manifestation of bronchiectasis is extremely rare. We report a case of a sudden hemothorax due to exacerbation of clinically latent bronchiectasis under a direct oral anticoagulant.

Case presentation

A 77-year-old woman presented with chest pain and a fever noted since the day before. She had stage G3 chronic kidney disease and received edoxaban for paroxysmal atrial fibrillation. She had no history of trauma or respiratory symptoms. A chest computed tomography revealed a mass with a surrounding opacity in the right lower lobe with a pleural effusion. Conservative treatment was chosen because of the stable vital signs and her respiratory condition. Her oxygen saturation dropped 7 h later with progressive anemia. Repeated chest computed tomography showed a worsening pulmonary opacity and pleural effusion. She underwent a right lower lobectomy successfully. The histopathological findings suggested that the preceding infection of the subpleural focal bronchiectasis caused the bleeding. In addition, a steep caliber change between the subpleural focal bronchiectasis and proximal normal branch may have caused an intraluminal pressure gradient resulting in a peripheral discharge causing a pleural rupture with a hemothorax.

Conclusion

The sudden hemothorax could have been the initial manifestation of bronchiectasis. Particular attention should be paid to peripherally localized bronchiectasis even if it is without any clinical symptoms, especially in patients with a comorbidity such as a susceptibility to infections and the use of direct oral anticoagulants.
Is colonial heritage negative or not so much? Debating heritage discourses and selective interpretation of Kulangsu, China
Authors: Wei Ran , Wang Fang
Published: September 2022

Heritage is in essence dissonant, especially colonial heritage in postcolonial nations. Via questionnaire surveys and interviews, this study investigates Kulangsu in Xiamen, China, a colonial heritage site mainly developed in the 19th and 20th centuries, to unveil the local government’s authorised heritage discourse (AHD) of the site and how tourists perceive the colonial past of Kulangsu and construct their own heritage discourse(s). Results show that, when considering the colonial history of the site, neither the AHD promoted by the authorities nor the tourists’ lay discourses are necessarily negative. However, tension implicitly arises between the tourists’ demand for comprehensive heritage information and the authorities’ selective interpretation of the site. Although the AHD affects lay discourses to some extent, most tourists expect the authorities to present more complete and neutral information about heritage so they can reflect and forge their own conception of colonial legacies. From a critical heritage studies perspective, this tension reflects the power imbalance between the authorities and the tourists and reminds the authorities and heritage experts to rethink heritage tourism and conservation in terms of heritage interpretation. This paper, therefore, calls for additional reflection on the legitimacy of selective interpretation, which implicates a complex process of intricate reasoning that is underpinned by the power imbalance between the authorities and the tourists, ultimately resulting in an AHD.
Dependence of effective permeability on pore pressure gradient at low flow rates in low-permeability limestone
Authors: Baryshnikov Nikolay A. , Zenchenko Evgeny V. , Turuntayev Sergey B.
Published: September 2022

Many researchers note a nonlinearity of flow in tight rock samples at low rates. The effects include changes in apparent permeability with pore pressure gradient and so-called threshold gradients, below which low flow or no flow occurs. It is believed that these effects may be related to the influence of adhesive layers with altered properties at the interfaces between liquid and solid phases. For low-permeable rocks, the estimation of reservoir permeability without taking into account the nonlinearity of the flow can lead to significant errors. An account of the flow nonlinearity also can downgrade the reservoir productivity estimation and may result in underestimation of stationary oil zone appearances. Conventional methods for studying fluid flows in porous rocks are poorly suited for studying their permeability when approaching zero flow rates because of the lack of accuracy. Such studies also require a special approach for the interpretation of the data obtained. At the same time, there is a lack of discussion of the appropriate experimental technique in the publications known. Our goal was to develop a technique suitable for studying the flow nonlinearity at extremely low flow rates. Using the developed experimental technique, we carried out three series of consecutive tests on three similar limestone core samples. The samples were taken from the aquifer; however, their porosity and permeability are similar to the typical parameters of a tight oil reservoir. During the test series, we observed the change in the deviation from the linear Darcy’s law over a long time. We realized that in the sample with the most pronounced deviation from linear flow, there was a most significant decrease in net permeability in the entire series. We believe that our method can provide more precise evaluation of the permeability of tight rocks at the near real flow rate.
Tri-linear representations for the Laser Interferometer Space Antenna
Authors: Andersson Fredrik , Riegger Franziska , Ferraioli Luigi , Giardini Domenico , Robertsson Johan
Published: September 2022

The Laser Interferometer Space Antenna (LISA) is a space-borne observatory of gravitational waves to be launched by ESA and NASA in the 2030s. Interferometric measurements are made between three spacecraft orbiting the Sun. The measurements are dependent on the geometric information due to the relative locations between the spacecraft as well as the intrinsic parameters of the astrophysical objects that generate the gravitational waves. We show that the measurements of mildly chirping gravitational waves can be approximated by means of a tri-linear representation, where the geometric information about the location of the observed object as well as that of the spacecraft locations are separated by different factors. We discuss that for low frequencies the relative approximation error is proportional to the square of the signal’s carrier frequency and illustrate this accuracy in numerical experiments. For the sake of illustration, we outline a simple algorithm for extracting parameters from the observed gravitational waves.
Correlation of the Modified Japanese Orthopedic Association With Functional and Quality-of-Life Outcomes After Surgery for Degenerative Cervical Myelopathy: A Quality Outcomes Database Study
Authors: Yee Timothy J. , Upadhyaya Cheerag , Coric Domagoj , Potts Eric A. , Bisson Erica F. , Turner Jay , Knightly Jack J. , Fu Kai-Ming , Foley Kevin T. , Tumialan Luis , Shaffrey Mark E. , Bydon Mohamad , Mummaneni Praveen , Chou Dean , Chan Andrew , Meyer Scott , Asher Anthony L. , Shaffrey Christopher , Gottfried Oren N. , Than Khoi D. , Wang Michael Y. , Buchholz Avery L. , Haid Regis , Park Paul
Published: September 2022

BACKGROUND:

The modified Japanese Orthopedic Association (mJOA) score is a widely used and validated metric for assessing severity of myelopathy. Its relationship to functional and quality-of-life outcomes after surgery has not been fully described.

OBJECTIVE:

To quantify the association of the mJOA with the Neck Disability Index (NDI) and EuroQol-5 Dimension (EQ-5D) after surgery for degenerative cervical myelopathy.

METHODS:

The cervical module of the prospectively enrolled Quality Outcomes Database was queried retrospectively for adult patients who underwent single-stage degenerative cervical myelopathy surgery. The mJOA score, NDI, and EQ-5D were assessed preoperatively and 3 and 12 months postoperatively. Improvement in mJOA was used as the independent variable in univariate and multivariable linear and logistic regression models.

RESULTS:

Across 14 centers, 1121 patients were identified, mean age 60.6 ± 11.8 years, and 52.5% male. Anterior-only operations were performed in 772 patients (68.9%). By univariate linear regression, improvements in mJOA were associated with improvements in NDI and EQ-5D at 3 and 12 months postoperatively (all P < .0001) and with improvements in the 10 NDI items individually. These findings were similar in multivariable regression incorporating potential confounders. The Pearson correlation coefficients for changes in mJOA with changes in NDI were −0.31 and −0.38 at 3 and 12 months postoperatively. The Pearson correlation coefficients for changes in mJOA with changes in EQ-5D were 0.29 and 0.34 at 3 and 12 months.

CONCLUSION:

Improvements in mJOA correlated weakly with improvements in NDI and EQ-5D, suggesting that changes in mJOA may not be a suitable proxy for functional and quality-of-life outcomes.
Lobbing dla Ukrainy w Europie międzywojennej: Ukraińskie Biuro Prasowe w Londynie oraz jego konkurenci polityczni (do roku 1932)
Authors: Zięba Andrzej A.
Published: September 2022

Książka Lobbing dla Ukrainy w Europie międzywojennej. Ukraińskie Biuro Prasowe w Londynie oraz jego konkurenci polityczni (do roku 1932) koncentruje się na słabo dotychczas opracowanym aspekcie sprawy ukraińskiej w polityce międzynarodowej w pierwszej połowie XX wieku. Ukazuje trudne i zawiłe drogi, którymi naród pozostaJący na marginesie politycznym świata przedzierał się do świadomości jego elit, usiłując zdobyć akceptację mocarstw, stać się obiektem i podmiotem regionalnych, a nawet globalnych kalkulacji politycznych. Charakteryzuje aktorów tych zmagań, postacie lobbystów - nieraz zapomniane, zlekcewazżne przez historiografię ukraińską, chętniejszą do opiewania czynów bojowych i rewolucyjnych. Analizuje cele sił zewnętrznych, żywotnie zainteresowanych lobbingiem ukraińskim: Niemiec i Związku Sowieckiego, polskich prometetstów, brytyJskich „ukrainofilów", żydostwa „białej" emigracji rosyjskiej, i zaplątanych tu malutkiej Litwy i ambitnej Czechosłowacji. Autor rekonstruuje badane zjawisko lobbingu i szuka odpowiedzi na pytanie o Jego konsekwencje.
Disjunctive Rule Lists
Authors: Ragodos Ronilo , Wang Tong
Published: September 2022

In this study, we present an interpretable model, disjunctive rule list (DisRL) for regression. This research is motivated by the increasing need for model interpretability, especially in high-stakes decisions such as medicine, where decisions are made on or related to humans. DisRL is a generalized form of rule lists. A DisRL model consists of a list of disjunctive rules embedded in an if-else logic structure that stratifies the data space. Compared with traditional decision trees and other rule list models in the literature that stratify the feature space with single itemsets (an itemset is a conjunction of conditions), each disjunctive rule in DisRL uses a set of itemsets to collectively cover a subregion in the feature space. In addition, a DisRL model is constructed under a global objective that balances the predictive performance and model complexity. To train a DisRL model, we devise a hierarchical stochastic local search algorithm that exploits the properties of DisRL’s unique structure to improve search efficiency. The algorithm adopts the main structure of simulated annealing and customizes the proposing strategy for faster convergence. Meanwhile, the algorithm uses a prefix bound to locate a subset of the search area, effectively pruning the search space at each iteration. An ablation study shows the effectiveness of this strategy in pruning the search space. Experiments on public benchmark datasets demonstrate that DisRL outperforms baseline interpretable models, including decision trees and other rule-based regressors.

History: Accepted by J. Paul Brooks, Area Editor for Applications in Biology, Medicine, & Healthcare.

Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplementary Information [ https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.1242 ] or is available from the IJOC GitHub software repository ( https://github.com/INFORMSJoC ) at [ http://dx.doi.org/10.5281/zenodo.6954927 ].
Fair Integral Network Flows
Authors: Frank András , Murota Kazuo
Published: September 2022

A strongly polynomial algorithm is developed for finding an integer-valued feasible st-flow of a given flow amount, which is decreasingly minimal on a specified subset F of edges in the sense that the largest flow value on F is as small as possible; within this, the second largest flow value on F is as small as possible; within this, the third largest flow value on F is as small as possible, and so on. A characterization of the set of these st-flows gives rise to an algorithm to compute a cheapest F-decreasingly minimal integer-valued feasible st-flow of given flow amount. Decreasing minimality is a possible formal way to capture the intuitive notion of fairness.

Funding: This work was supported by JSPS KAKENHI [Grants JP20K11697, JP26280004] and the National Research, Development, and Innovation Fund of Hungary [Grant NKFI-128673].
Exploring nurses' experiences of caring for patients participating in cancer clinical trials
Authors: Hood Ben
Published: September 2022

Aims:

Drawing on the experiences of cancer research nurses (CRNs) from the Cancer Research UK Excellence in Research Programme, this article aims to provide an insight into managing cancer patients' expectations of participating in clinical trials. It also outlines what CRNs consider are the key elements when supporting patients through side-effect management.

Method:

Through group work and discussions, CRNs' reflective experiences were captured by workshop facilitators around three topics by exploring nurses' experiences of caring for patients participating in cancer clinical trials. Reflective CRN experiences for each of the three topics were reviewed and themes were developed by the author, who also facilitated this workshop.

Results:

Developing relationships, patient education and effective communication were all identified as important factors when helping to manage patient expectations and aid side-effect management.

Conclusion:

The findings, based on CRN experiences, give an understanding of aspects of the role that nurses have within cancer clinical trials, what patient expectations of clinical trial are and strategies on how best to support patients within this area of nursing.
COVID-19 Social Media Infodemic: The New Media Literacy Level and the Ability to Recognize Fake News Among Cebu City Young Adults
Authors:   University of the Philippines Cebu, College of Social Sciences, Philippines, Maningo Clyde , Dacuno Jester ,   University of the Philippines Cebu, College of Social Sciences, Philippines, Del Rosario Noah ,   University of the Philippines Cebu, College of Social Sciences, Philippines, Dumaguit Reanit ,   University of the Philippines Cebu, College of Social Sciences, Philippines, Garay Cezannelle ,   University of the Philippines Cebu, College of Social Sciences, Philippines, Villahermosa Hermelie ,   University of the Philippines Cebu, College of Social Sciences, Philippines
Published: September 2022

The downside of the integrative aspect of the digital space is how easily fake news can propagate which jeopardized the regulation and control measures of the COVID-19 pandemic. While existing literature expounds on the nature of infodemic phenomenon, recent curiosities lack the exploration of the contributing factors that led to the inability to recognize fake news on social media as it corresponds to the New Media Literacy (NML) levels. NML allows adaptation to technological advancement as it constantly evolves with great sophistication. Anchored from this gap, the study employs a quantitative research design where 385 respondents from Cebu City—a highly urbanized city in the Philippines—were asked to answer a three-part survey questionnaire. The findings purport that a high percentage of respondents can distinguish legitimate from fake news and take proactive measures in reporting or resharing the posts. Moreover, the study reveals that the respondents have high NML levels, particularly in functional prosuming and consuming aspects, which the study probed according to the demographic factors. The salient discussion then revolves around the low critical outcomes of prosuming and consuming NML aspects to push for educational policy formulation methods with interpretive social-scientific approaches. This reinforces the post-truth lens in expanding the fields of concerns arising from the infodemic phenomenon. Furthermore, recommendatory measures are provided in the Philippine educational system— that may be reintegrated into the dimensions of policy theories for educational policy evaluation to probe different areas of improvement in the Media and Information Literacy of the K-12 curriculum. Keywords: COVID-19, fake news, infodemic, new media literacy, post-truths
Cavity-resonator integrated bi-atom grating coupler for enhanced second-harmonic generation
Authors: Fehrembach Anne-Laure , Popov Evgueni , Hemsley Elizabeth , Monmayrant Antoine , Gauthier-Lafaye Olivier , Calvez Stéphane
Published: September 2022

We report on the design of cavity-resonator integrated grating couplers for second-harmonic generation. The key point is that the base pattern of our grating coupler (GC) is made of two ridges with different widths (bi-atom). Thus, we reach extremely high Q-factors (above 105) with structures whose fabrication is not challenging, since the bi-atom base pattern is close to that of the surrounded distributed Bragg reflectors (DBR). Yet, the parameters of the structure have to be chosen cautiously to reduce the transition losses between each section (GC, DBR). We numerically demonstrate conversion efficiencies η of several tenths per Watt, even doubled when we include a phase-matching grating within the structuration. Such efficiencies are comparable to those obtained with waveguides and nano-resonators.
Thermally assisted fabrication of nonlinear photonic structures in lithium niobate with femtosecond laser pulses
Authors: Imbrock Jörg , Szalek Dominik , Laubrock Simon , Hanafi Haissam , Denz Cornelia
Published: September 2022

Engineered domain structures play an essential role in nonlinear optics for quasi-phase-matched parametric processes. Pyroelectric field-assisted domain inversion with focused femtosecond laser pulses is a promising approach to create arbitrary two-dimensional nonlinear photonic structures in a large volume without externally applied electrical fields. We fabricate lattices of ferroelectric domains by patterning lithium niobate crystals with femtosecond laser pulses and then heating them to elevated temperatures. After cooling to room temperature, domains form below and above the laser-induced seeds. We investigate the effect of temperature and seed spacing on the number and size of inverted domains. In a temperature range of 220 °C-300 °C all domains are inverted in a two-dimensional lattice with periods of 15 µm × 6.3 µm. Smaller lattice periods result in a smaller fraction of inverted domains. Measurements with conducting, nonconducting, and short-circuited crystal surfaces reveal the influence of surface charges during the domain formation process. From the obtained domain widths and spacings, we calculate the effective nonlinear coefficient of quasi-phase-matched second-harmonic generation in two-dimensional nonlinear photonic structures.
Fabry-Pérot resonant avalanche-mode silicon LEDs for tunable narrow-band emission
Authors: Dutta Satadal , Verbiest Gerard J.
Published: September 2022

We report on the effect of Fabry-Pérot (FP) resonance on hot-carrier electroluminescence (EL) spectra and the optical power efficiencies of silicon (Si) avalanche-mode (AM) LEDs in the wavelength range from 500 nm to 950 nm. The LEDs, fabricated in a silicon-on-insulator photonics technology, consist of symmetric p-n junctions placed within a 0.21 µm thick Si micro-ring of varying width and radius. We show that the peak wavelength in the EL-spectra can be tuned within a range of 100 nm by varying the ring width from 0.16 µm to 0.30 µm, which is explained by FP resonance. The measured EL-spectra features relatively narrow bands (with a spectral width of ∼50 nm) with high intensities compared to conventional Si AMLEDs. By varying the ring radius and using a high doping level, we obtain a record high optical power efficiency of 3.2×10−5. Our work is a breakthrough in engineering the EL spectrum of Si, foreseen to benefit the performance of Si-integrated optical interconnects and sensors.
Non-local scattering control in coupled resonator networks
Authors: Román-García D. A. , Maldonado-Villamizar F. H. , Jaramillo-Ávila B. , Rodríguez-Lara B. M.
Published: September 2022

We demonstrate scattering control of Gaussian-like wave packets propagating with constant envelope velocity and invariant waist through coupled resonator optical waveguides (CROW) via an external resonator coupled to multiple sites of the CROW. We calculate the analytical reflectance and transmittance using standard scattering methods from waveguide quantum electrodynamics and show it is possible to approximate them for an external resonator detuned to the CROW. Our analytical and approximate results are in good agreement with numerical simulations. We engineer various configurations using an external resonator coupled to two sites of a CROW to show light trapping with effective exponential decay between the coupling sites, wave packet splitting into two pairs of identical Gaussian-like wave packets, and a non-local Mach-Zehnder interferometer.
Three-element, self-starting Kerr-lens-modelocked 1-GHz Ti:sapphire oscillator pumped by a single laser diode
Authors: Ostapenko Hanna , Mitchell Toby , Castro-Marin Pablo , Reid Derryck T.
Published: September 2022

We present a Kerr-lens-modelocked, three-element, diode-pumped Ti:sapphire laser producing 111-fs pulses at a repetition frequency of 1.02 GHz. Self-starting soliton-modelocked operation with an output power of 106 mW was obtained when the laser was pumped at 1.0 W with a single 527-nm laser diode. The output exhibits a relative intensity noise of 0.06% (1 Hz – 1 MHz) and locking of the repetition rate to an external reference is demonstrated with a phase error of 1.7 mrad (1 Hz–1 MHz). The simplicity of the laser makes it an attractive candidate as a module for integration into larger systems.
Homogenization and reduction of the roughness of polished sapphire surfaces via inert gas plasma post-processing
Authors: Gerhard Christoph , Tasche Daniel
Published: September 2022

In this paper, we report on the post-processing of classically precision polished sapphire surfaces by means of a dielectric barrier discharge plasma at atmospheric pressure. Here, the lateral distribution of roughness values over the surface was significantly reduced, leading to a higher lateral homogeneity. This effect is shown by a decrease in the standard deviation of the roughness values measured at different positions over the sample surface where an overall plasma-induced reduction by a factor of 8.7 was achieved. Moreover, the residual roughness was notably decreased by a mean factor of up to 2.9 to merely a few angstrom. The obtained results are of high interest for the enhancement of large-scale optical components made of sapphire, especially for UV or laser applications. This is finally visualized by the comparison of the total integrated scatter values calculated for untreated and post-processed surfaces.
MicrobiomeCensus estimates human population sizes from wastewater samples based on inter-individual variability in gut microbiomes
Authors: Zhang Lin , Chen Likai , Yu Xiaoqian (Annie) , Duvallet Claire , Isazadeh Siavash , Dai Chengzhen , Park Shinkyu , Frois-Moniz Katya , Duarte Fabio , Ratti Carlo , Alm Eric J. , Ling Fangqiong
Published: September 2022

The metagenome embedded in urban sewage is an attractive new data source to understand urban ecology and assess human health status at scales beyond a single host. Analyzing the viral fraction of wastewater in the ongoing COVID-19 pandemic has shown the potential of wastewater as aggregated samples for early detection, prevalence monitoring, and variant identification of human diseases in large populations. However, using census-based population size instead of real-time population estimates can mislead the interpretation of data acquired from sewage, hindering assessment of representativeness, inference of prevalence, or comparisons of taxa across sites. Here, we show that taxon abundance and sub-species diversisty in gut-associated microbiomes are new feature space to utilize for human population estimation. Using a population-scale human gut microbiome sample of over 1,100 people, we found that taxon-abundance distributions of gut-associated multi-person microbiomes exhibited generalizable relationships with respect to human population size. Here and throughout this paper, the human population size is essentially the sample size from the wastewater sample. We present a new algorithm, MicrobiomeCensus, for estimating human population size from sewage samples. MicrobiomeCensus harnesses the inter-individual variability in human gut microbiomes and performs maximum likelihood estimation based on simultaneous deviation of multiple taxa’s relative abundances from their population means. MicrobiomeCensus outperformed generic algorithms in data-driven simulation benchmarks and detected population size differences in field data. New theorems are provided to justify our approach. This research provides a mathematical framework for inferring population sizes in real time from sewage samples, paving the way for more accurate ecological and public health studies utilizing the sewage metagenome.
An expert judgment model to predict early stages of the COVID-19 pandemic in the United States
Authors: McAndrew Thomas , Reich Nicholas G.
Published: September 2022

From February to May 2020, experts in the modeling of infectious disease provided quantitative predictions and estimates of trends in the emerging COVID-19 pandemic in a series of 13 surveys. Data on existing transmission patterns were sparse when the pandemic began, but experts synthesized information available to them to provide quantitative, judgment-based assessments of the current and future state of the pandemic. We aggregated expert predictions into a single “linear pool” by taking an equally weighted average of their probabilistic statements. At a time when few computational models made public estimates or predictions about the pandemic, expert judgment provided (a) falsifiable predictions of short- and long-term pandemic outcomes related to reported COVID-19 cases, hospitalizations, and deaths, (b) estimates of latent viral transmission, and (c) counterfactual assessments of pandemic trajectories under different scenarios. The linear pool approach of aggregating expert predictions provided more consistently accurate predictions than any individual expert, although the predictive accuracy of a linear pool rarely provided the most accurate prediction. This work highlights the importance that an expert linear pool could play in flexibly assessing a wide array of risks early in future emerging outbreaks, especially in settings where available data cannot yet support data-driven computational modeling.
Chemical contaminant levels in edible seaweeds of the Salish Sea and implications for their consumption
Authors: Hahn Jennifer L. , Van Alstyne Kathryn L. , Gaydos Joseph K. , Wallis Lindsay K. , West James E. , Hollenhorst Steven J. , Ylitalo Gina M. , Poppenga Robert H. , Bolton Jennie L. , McBride David E. , Sofield Ruth M.
Published: September 2022

Despite growing interest in edible seaweeds, there is limited information on seaweed chemical contaminant levels in the Salish Sea. Without this knowledge, health-based consumption advisories can not be determined for consumers that include Tribes and First Nations, Asian and Pacific Islander community members, and recreational harvesters. We measured contaminant concentrations in edible seaweeds (Fucus distichus,F.spiralis, andNereocystis luetkeana) from 43 locations in the Salish Sea. Metals were analyzed in all samples, and 94 persistent organic pollutants (POPs) (i.e. 40 PCBs, 15 PBDEs, 17 PCDD/Fs, and 22 organochlorine pesticides) and 51 PAHs were analyzed inFucusspp. We compared concentrations of contaminants to human health-based screening levels calculated from the USEPA and to international limits. We then worked with six focal contaminants that either exceeded screening levels or international limits (Cd, total Hg, Pb, benzo[a]pyrene [BaP], and PCBs) or are of regional interest (total As). USEPA cancer-based screening levels were exceeded in 30 samples for the PCBs and two samples for BaP. Cadmium concentrations did not exceed the USEPA noncancer-based screening level but did exceed international limits at all sites. Lead exceeded international limits at three sites. Because there are no screening levels for total Hg and total As, and to be conservative, we made comparisons to methyl Hg and inorganic As screening levels. All samples were below the methyl Hg and above the inorganic As screening levels. Without knowledge of the As speciation, we cannot assess the health risk associated with the As. While seaweed was the focus, we did not consider contaminant exposure from consuming other foods. Other chemicals, such as contaminants of emerging concern (e.g., PFAS, pharmaceuticals and personal care products), should also be considered. Additionally, although we focused on toxicological aspects, there are cultural and health benefits of seaweed use that may affect consumer choice.
Versatile seamless DNA vector production in E. coli using enhanced phage lambda integrase
Authors: Roy Suki , Peter Sabrina , Dröge Peter
Published: September 2022

Seamless DNA vectors derived from bacterial plasmids are devoid of bacterial genetic elements and represent attractive alternatives for biomedical applications including DNA vaccines. Larger scale production of seamless vectors employs engineered Escherichia coli strains in order to enable tightly regulated expression of site-specific DNA recombinases which precisely delete unwanted sequences from bacterial plasmids. As a novel component of a developing lambda integrase genome editing platform, we describe here strain MG1655-ISC as a means to easily produce different scales of seamless vectors, ranging in size from a few hundred base pairs to more than ten kilo base pairs. Since we employed an engineered lambda integrase that is able to efficiently recombine pairs of DNA crossover sites that differ in sequence, the resulting seamless vectors will be useful for subsequent genome editing in higher eukaryotes to accommodate variations in target site sequences. Future inclusion of single cognate sites for other genome targeting systems could enable modularity. These features, together with the demonstrated simplicity of in vivo seamless vector production, add to their utility in the biomedical space.