bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional benefits of the double flap technique after proximal gastrectomy for gastric cancer
Authors: Saze Zenichiro , Kase Koji , Nakano Hiroshi , Yamauchi Naoto , Kaneta Akinao , Watanabe Yohei , Hanayama Hiroyuki , Hayase Suguru , Momma Tomoyuki , Kono Koji
Published: November 2021

Background

Proximal gastrectomy is a widely performed procedure that has become more common with an increasing number of proximal gastric cancer cases. Several types of reconstructive procedures after proximal gastrectomy have been developed, and it remains controversial which procedure is the most advantageous with regard to the preservation of postoperative gastric stump function and nutritional status. In the present study, we retrospectively analyzed reconstructive procedures in a consecutive case series for proximal gastrectomy, primarily focusing on postoperative body weight maintenance, nutritional status, and gastric remnant functional preservation.

Methods

We enrolled 69 patients who had undergone proximal gastrectomy for gastric cancer in our institute between 2005 and 2020. Short-term complications, preservation of gastric remnant functions, nutritional status, and post-operative weight changes were compared.

Results

After proximal gastrectomy, the numbers of patients who underwent direct esophago-gastrostomy, jejunal interposition, double tract reconstruction, and the double flap technique were 9, 10, 14, and 36, respectively. The patients in whom the double flap technique was performed suffered no reflux esophagitis after surgery. Prevalence of gastric residual at 12 months after surgery was lowest in the double flap technique group. Moreover, the double flap technique group had a better tendency regarding post-operative changes of serum albumin ratios. Furthermore, the post-operative body weight change ratio of the double flap technique group was smallest among all groups and was significantly better than that of the double tract group.

Conclusions

The double flap technique after proximal gastrectomy was considered the most effective technique for reconstruction which leads to better bodyweight maintenance, and results in less reflux esophagitis.
The impact of patient delirium in the intensive care unit: patterns of anxiety symptoms in family caregivers
Authors: Poulin Therese G. , Krewulak Karla D. , Rosgen Brianna K. , Stelfox Henry T. , Fiest Kirsten M. , Moss Stephana J.
Published: November 2021

Background

The purpose of this study was to examine the association of patient delirium in the intensive care unit (ICU) with patterns of anxiety symptoms in family caregivers when delirium was determined by clinical assessment and family-administered delirium detection.

Methods

In this cross-sectional study, consecutive adult patients anticipated to remain in the ICU for longer than 24 h were eligible for participation given at least one present family caregiver (e.g., spouse, friend) provided informed consent (to be enrolled as a dyad) and were eligible for delirium detection (i.e., Richmond Agitation-Sedation Scale score ≥ − 3). Generalized Anxiety Disorder-7 (GAD-7) was used to assess self-reported symptoms of anxiety. Clinical assessment (Confusion Assessment Method for ICU, CAM-ICU) and family-administered delirium detection (Sour Seven) were completed once daily for up to five days.

Results

We included 147 family caregivers; the mean age was 54.3 years (standard deviation [SD] 14.3 years) and 74% (n = 129) were female. Fifty (34% [95% confidence interval [CI] 26.4–42.2]) caregivers experienced clinically significant symptoms of anxiety (median GAD-7 score 16.0 [interquartile range 6]). The most prevalent symptoms of anxiety were “Feeling nervous, anxious or on edge” (96.0% [95%CI 85.2–99.0]); “Not being able to stop or control worrying” (88.0% [95%CI 75.6–94.5]; “Worrying too much about different things” and “Feeling afraid as if something awful might happen” (84.0% [95%CI 71.0–91.8], for both). Family caregivers of critically ill adults with delirium were significantly more likely to report “Worrying too much about different things” more than half of the time (CAM-ICU, Odds Ratio [OR] 2.27 [95%CI 1.04–4.91]; Sour Seven, OR 2.28 [95%CI 1.00–5.23]).

Conclusions

Family caregivers of critically ill adults with delirium frequently experience clinically significant anxiety and are significantly more likely to report frequently worrying too much about different things. Future work is needed to develop mental health interventions for the diversity of anxiety symptoms experienced by family members of critically ill patients.

Trial registration

This study is registered on ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03379129).
Evaluating the structural reform of outpatient psychotherapy in Germany (ES-RiP trial) - a qualitative study of provider perspectives
Authors: Poß-Doering Regina , Hegelow Martin , Borchers Milena , Hartmann Mechthild , Kruse Johannes , Kampling Hanna , Heuft Gereon , Spitzer Carsten , Wild Beate , Szecsenyi Joachim , Friederich Hans-Christoph
Published: November 2021

Background

Access to outpatient mental healthcare can be challenging for patients. In Germany, a national structural reform was implemented in 2017 to accelerate and enhance access to outpatient psychotherapy and reduce waiting times. During the first phase of the study ‘Evaluation of a structural reform of the outpatient psychotherapy guideline (ES-RiP)’ and embedded into a process evaluation, the implementation was to be evaluated through assessing general practitioners’ (GPs) and psychotherapists’ (PTs) perspectives regarding utilization of provided new measures, and perceived potential for optimization. Particular focus was on patients with a comorbidity of mental disorders and chronic physical conditions (cMPs).

Methods

This exploratory cross-sectional qualitative study used on-site and online focus group discussions and semi-structured telephone interviews with GPs and outpatient PTs. Generated data were analyzed using thematic framework analysis. Descriptive statistics were used to analyze participant characteristics collected via a socio-demographic questionnaire.

Results

Perspectives on the structural reform were heterogenous. GPs and PTs considered the component of timely initial psychotherapeutic assessment consultations beneficial. GPs disapproved of their deficits in detailed information about the structural reform and exchange with outpatient PTs. Improvement suggestions included structured short information exchange and joint quality circles. The overall number of available outpatient PTs in rural areas was perceived as insufficient. For patients with cMPs, GPs saw patient barriers for therapy access and continuity in low intrinsic motivation, physical impediments and older age. PTs also saw patient challenges regarding low intrinsic motivation and keeping scheduled appointments. They considered post-reform administrative efforts to be high and reported that the regulations (conformity) lead to planning difficulties and financial losses. Reform elements were tailored to fit in with PTs key therapy areas. Stronger networking and joint lectures were suggested as remedy for the currently still limited exchange with GPs. Unlike the GPs, PTs emphasized that accepting patients into psychotherapeutic treatment was independent of a possibly present chronic physical disease.

Conclusions

The findings contribute to understanding the integration of the delivered structural reform into daily care processes and provide an indication about reached targets and potential improvements. Further phases of the ES-RiP study can build on the findings and broaden insights.

Trial registration

Registration-ID DRKS00020344 (DRKS German Register of Clinical Trials.
Length of exposure to long working hours and night work and risk of sickness absence: a register-based cohort study
Authors: Peutere Laura , Rosenström Tom , Koskinen Aki , Härmä Mikko , Kivimäki Mika , Virtanen Marianna , Ervasti Jenni , Ropponen Annina
Published: November 2021

Background

There is inconsistent evidence that long working hours and night work are risk factors for sickness absence, but few studies have considered variation in the length of exposure time window as a potential source of mixed findings. We examined whether the association of long working hours and night work with sickness absence is dependent on the length of exposure to the working hour characteristics.

Methods

We analysed records of working hours, night work and sickness absence for a cohort of 9226 employees in one hospital district in Finland between 2008 and 2019. The exposure time windows ranged from 10 to 180 days, and we used Cox’s proportional hazards models with time-dependent exposures to analyse the associations between working-hour characteristics and subsequent sickness absence.

Results

Longer working hours for a period of 10 to 30 days was not associated with the risk of sickness absence whereas longer working hours for a period of 40 to 180 days was associated with a lower risk of sickness absence. Irrespective of exposure time window, night work was not associated with sickness absence.

Conclusions

It is important to consider the length of exposure time window when examining associations between long working hours and sickness absence, whereas the association between night work and sickness absence is not similarly sensitive to exposure times.
Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data
Authors: Sato Noriko , Fudono Ayako , Imai Chihiro , Takimoto Hidemi , Tarui Iori , Aoyama Tomoko , Yago Satoshi , Okamitsu Motoko , Mizutani Shuki , Miyasaka Naoyuki
Published: November 2021

Background

Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP.

Methods

Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only “vasculature-related” BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity.

Results

We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of “vasculature-related” BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation.

Conclusions

Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.
ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
Authors: Mao Weipu , Wang Keyi , Xu Bin , Zhang Hui , Sun Si , Hu Qiang , Zhang Lei , Liu Chunhui , Chen Shuqiu , Wu Jianping , Chen Ming , Li Wei , Peng Bo
Published: November 2021

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.
Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis
Authors: Wu Hanglin , Zhang Songying , Lin Xiaona , He Jing , Wang Shasha , Zhou Ping
Published: November 2021

Background

Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown.

Methods

Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Results

We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42–0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40–0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79–1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34–0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size.

Conclusion

Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.
Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study
Authors: Shoji Makoto , Matsui Taiju , Tanaka Hideaki , Nomura Kosuke , Tsujita Hiroaki , Kodama Yusuke , Koba Shinji , Kobayashi Youichi , Shinke Toshiro
Published: November 2021

Background

The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined.

Methods

This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured.

Results

The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000–1.036, p = 0.034).

Conclusions

These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.
GLRX5-associated [Fe-S] cluster biogenesis disorder: further characterisation of the neurological phenotype and long-term outcome
Authors: Sankaran Bindu Parayil , Gupta Sachin , Tchan Michel , Devanapalli Beena , Rahman Yusof , Procopis Peter , Bhattacharya Kaustuv
Published: November 2021

Background

Identification and characterisation of monogenic causes of complex neurological phenotypes are important for genetic counselling and prognostication. Bi-allelic pathogenic variants in the gene encoding GLRX5, a protein involved in the early steps of Fe-S cluster biogenesis, are rare and cause two distinct phenotypes: isolated sideroblastic anemia and a neurological phenotype with variant non-ketotic hyperglycinemia. In this study, we analysed the evolution of clinical and MRI findings and long-term outcome of patients with GLRX5 mutations.

Methods

Four patients from three Australian families of Lebanese descent were identified. All patients presented in childhood and were followed up into adult life through multiple clinical assessments. All were prescribed sodium benzoate.

Results

All patients (all females, age range 18–56 years) showed a complex neurological phenotype characterised by varying combinations of spastic paraparesis, length-dependent motor/sensory-motor axonal polyneuropathy, and psychiatric disturbances with variable intellectual disability. All had non-ketotic hyperglycinemia and a homozygous pathogenic c.151_153delAAG (p.K51del) change in GLRX5. Motor disability gradually progressed reaching moderate disability during adolescence and moderately severe disability during adult life. The major MRI finding was the upper cervical spinal cord signal changes with contrast enhancement noted in all and additional leukoencephalopathy in one. On follow up MRI, the white matter lesions diminished on a subsequent scan and then remained static over time. The spinal cord showed gliotic changes. Two patients have previously demonstrated low pyruvate dehydrogenase complex deficiency but none had plasma lactate elevation, nor biochemical evidence of branch-chain keto-dehydrogenase deficiency. Glycine levels reduced in patients that tolerated sodium benzoate, possibly stabilising clinical manifestations.

Conclusions

This report demonstrates that the p.K51del GLRX5 variant causes a distinct and predictable neurological phenotype. The clinical assessments spanning from childhood to adult life enable physicians to infer the natural history of GLRX5 related neurological disorder. There may be widespread metabolic consequences, and optimal management is unknown.
A cluster RCT and process evaluation of an implementation optimisation intervention to promote parental engagement enrolment and attendance in a childhood obesity prevention programme: results of the Optimising Family Engagement in HENRY (OFTEN) trial
Authors: Bryant Maria , Burton Wendy , Collinson Michelle , Farrin Amanda , Nixon Jane , Stevens June , Roberts Kim , Foy Robbie , Rutter Harry , Copsey Bethan , Hartley Suzanne , Tubeuf Sandy , Brown Julia
Published: November 2021

Background

Poor and variable implementation of childhood obesity prevention programmes reduces their population impact and sustainability. We drew upon ethnographic work to develop a multi-level, theory-based implementation optimisation intervention. This intervention aimed to promote parental enrolment and attendance at HENRY (Health Exercise Nutrition for the Really Young), a UK community obesity prevention programme, by changing behaviours of children’s centre and local authority stakeholders.

Methods

We evaluated the effectiveness of the implementation optimisation intervention on HENRY programme enrolment and attendance over a 12-month implementation period in a cluster randomised controlled trial. We randomised 20 local government authorities (with 126 children’s centres) to HENRY plus the implementation optimisation intervention or to HENRY alone. Primary outcomes were (1) the proportion of centres enrolling at least eight parents per programme and (2) the proportion of centres with a minimum of 75% of parents attending at least five of eight sessions per programme. Trial analyses adjusted for stratification factors (pre-randomisation implementation of HENRY, local authority size, deprivation) and allowed for cluster design. A parallel mixed-methods process evaluation used qualitative interviews and routine monitoring to explain trial results.

Results

Neither primary outcome differed significantly between groups; 17.8% of intervention centres and 18.0% of control centres achieved the parent enrolment target (adjusted difference − 1.2%; 95% CI − 19.5%, 17.1%); 17.1% of intervention centres and 13.9% of control centres achieved the attendance target (adjusted difference 1.2%; 95% CI − 15.7%, 18.1%). Unexpectedly, the trial coincided with substantial national service restructuring, including centre closures and reduced funds. Some commissioning and management teams stopped or reduced delivery of both HENRY and the implementation optimisation intervention due to competing demands. Thus, at follow-up, HENRY programmes were delivered to approximately half the number of parents compared to baseline (n = 433 vs. 881).

Conclusions

During a period in which services were reduced by external policies, this first definitive trial found no evidence of effectiveness for an implementation optimisation intervention promoting parent enrolment to and attendance at an obesity prevention programme.

Trial registration

ClinicalTrials.govNCT02675699. Registered on 4 February 2016
Spatial patterns of insect herbivory within a forest landscape: the role of soil type and forest stratum
Authors: Shao Xinliang , Zhang Qin , Yang Xitian
Published: November 2021

Background

Insect herbivory has profound impacts on ecosystem processes and services. Although many efforts have been made to recognize the main drivers of insect herbivory at different scales, the results are inconsistent. One likely reason is that studies have insufficiently captured the spatially heterogeneous factors such as soil type and forest stratum within the stand that may significantly affect insect herbivory. In particular, there is a lack of studies that address the detailed spatial patterns of insect herbivory which are influenced by these factors.

Methods

We measured the detailed spatial patterns of insect herbivory on cork oak (Quercus variabilis Bl.) in response to soil type (gravel soil and loam) and forest stratum (the upper, lower, and sapling stratum), and correlated these patterns with a set of influencing factors (litter coverage, coverage of shrubs and herbs, soil nutrients, soil moisture, and leaf traits) in a forest landscape.

Results

Generally, insect herbivory was spatially heterogeneous within stands. Herbivory was significantly lower in gravel soil areas than in loam soil areas and the highest herbivory occurred in the lower stratum. However, there were also 41 individual plots in which the highest herbivory occurred in the upper stratum and 29 plots in which the highest herbivory occurred in the sapling stratum. There were significant differences in soil nutrient and water status between soil types, but no significant differences in leaf traits. The effects of forest stratum on leaf traits were also inconsistent with those on insect herbivory.

Conclusions

Leaf traits may not be the main factors influencing insect herbivory in the field. Soil type may have major effects on herbivory patterns by influencing litter coverage while higher coverage of shrubs and herbs may reduce herbivory in the sapling stratum. These findings may advance our understanding of tree-herbivore interactions in real-world situations and have important implications for the sustainable management of forest ecosystems.
Retinal abnormalities in universal eye screening of healthy, full-term newborn infants in Jakarta. The incidence and its risk factors: a pilot study
Authors: Sitorus Rita S. , Pambudy Indra Maharddhika , Rohsiswatmo Rinawati , Barliana Julie Dewi , Yulia Dian Estu , Widyahening Indah Suci
Published: November 2021

Aim

To screen for ocular abnormalities in healthy full-term newborn infants using wide-field digital imaging and to analyze factors associated with the findings.

Methods

A total of 1208 full-term newborn infants at a tertiary eye hospital (Cipto Mangunkusumo National Referral Hospital) and a district hospital in Jakarta (Koja Hospital) were enrolled to the study. All eligible newborns underwent fundus examination within 48 h after birth using the RetCam shuttle (Natus Medical Incorporated, USA). Retinal findings were documented and analyzed according to obstetric and neonatal risk factors.

Results

Of the 1208 newborn infants enrolled, ocular abnormalities were found in 150 infants (12.4%). Retinal hemorrhage (RH) was the most common finding (88%) in which 2.67% involved the macula, followed by chorioretinitis (4.67%). Univariate analysis showed caesarean section (C-section) (OR 0.27, 95% CI 0.18–0.41, p < 0.001) was a protective factor against RH, while prolonged labor increased the risk of developing RH (OR 1.84, 95% CI 1.24–2.72, p = 0.002). Further multivariate analysis showed similar protective association between C-section and risk of RH (OR 0.29, 95% CI 0.19–0.44, p < 0.001), while other risk factors were not.

Conclusions

Our study showed that universal eye screening in healthy neonates is beneficial in the early diagnosis, monitoring and treatment of ocular abnormalities such as retinal hemorrhage, chorioretinitis and retinoblastoma. Retinal hemorrhage is the most common ocular abnormality and is associated with the delivery method and the duration of labor. Universal eye screening is visual-saving and life-saving for neonates with chorioretinitis, retinoblastoma as well as other abnormalities and should be mandatory in newborn screening.
Northern spotted owl nesting forests as fire refugia: a 30-year synthesis of large wildfires
Authors: Lesmeister Damon B. , Davis Raymond J. , Sovern Stan G. , Yang Zhiqiang
Published: November 2021

Background

The northern spotted owl (Strix occidentalis caurina) is an Endangered Species Act-listed subspecies that requires coniferous forests with structurally complex and closed-canopy old-growth characteristics for nesting. With climate change, large wildfires are expected to become more common within the subspecies’ range and an increasing threat to these types of forests. Understanding fire severity patterns related to suitable nesting forest will be important to inform forest management that affects conservation and recovery. We examined the relationship between fire severity and suitable nesting forest in 472 large wildfires (> 200 ha) that occurred in the northern spotted owl range during 1987–2017. We mapped fire severities (unburned-low, moderate, high) within each fire using relative differenced normalized burn ratios and quantified differences in severity between pre-fire suitable nesting forest (edge and interior) and non-nesting forest. We also quantified these relationships within areas of three fire regimes (low severity, very frequent; mixed severity, frequent; high severity, infrequent).

Results

Averaged over all fires, the interior nesting forest burned at lower severity than edge or non-nesting forest. These relationships were consistent within the low severity, very frequent, and mixed severity, frequent fire regime areas. All forest types burned at similar severity within the high severity, infrequent fire regime. During two of the most active wildfire years that also had the largest wildfires occurring in rare and extreme weather conditions, we found a bimodal distribution of fire severity in all forest types. In those years, a higher amount—and proportion—of all forest types burned at high severity. Over the 30-year study, we found a strong positive trend in the proportion of wildfires that burned at high severity in the non-nesting forests, but not in the suitable nesting forest types.

Conclusions

Under most wildfire conditions, the microclimate of interior patches of suitable nesting forests likely mitigated fire severity and thus functioned as fire refugia (i.e., burning at lower severity than the surrounding landscape). With changing climate, the future of interior forest as fire refugia is unknown, but trends suggest older forests can dampen the effect of increased wildfire activity and be an important component of landscapes with fire resiliency.
Leaky waveguides in hydrocarbon reservoirs and their implications for oil banks detection
Authors: Felix Servin Jesus Manuel , Deffenbaugh Max
Published: November 2021

The presence of naturally occurring subsurface waveguides for electromagnetic (EM) waves has been previously documented. In particular, the mining industry recognized that a coal seam bounded by layers of conductive rock acts as a leaky waveguide. Consequently, the attenuation constant and phase shift of EM signals propagating through the coal layer are modulated by the thickness of the coal and the EM properties of the three layers forming the leaky waveguide. The radio imaging method was developed based on this discovery to characterize coal deposits. Recent studies have determined that guided waves can provide useful information about the subsurface. Structures with similar dimensions and EM properties are found in oil fields in the form of layers of evaporite (e.g., anhydrite) bounded by hydrocarbon reservoirs. To the best of our knowledge, the feasibility of exploiting such structures to characterize the interwell region has not been investigated extensively. We have conducted a theoretical analysis and 3D numerical simulations in the time and frequency domains to demonstrate that layered structures in oil fields can act as leaky waveguides and efficiently guide EM waves. Our results suggest that such structures substantially enhance the propagation of megahertz EM signals. Among multiple parameters evaluated, the conductivity of the layers has the most significant effect on signal attenuation, and thus its range of propagation. We estimated that EM signals of approximately 10 MHz can propagate several hundreds of meters through a layer of anhydrite in the presence of conductive bounding reservoirs. The received signals are not only affected by the properties of the anhydrite layer, but also by the properties of the bounding reservoirs, conferring sensitivity to changes in reservoir saturation. We conclude that this approach could be further developed to infer fluid saturation and especially to identify the presence of oil banks in water-flooded hydrocarbon reservoirs.
Geologic forward prospecting using improved tunnel-seismic-while-drilling method: A case study of the water supply project at Songhua River, Jilin, China
Authors: Li Shucai , Chen Lei , Liu Bin , Xu Xinji , Liu Lanbo , Chen Yangkang
Published: November 2021

Unexpected geologic heterogeneities in tunnel lines often cause safety issues and economic losses during excavation using tunnel boring machines (TBMs). Therefore, collecting geologic information ahead of the excavation front is important to prevent geologic disasters and ensure excavation safety. To predict the geologic conditions ahead of the TBM-excavated tunnel in the water supply project at the Songhua River in China, the tunnel-seismic-while-drilling (TSWD) method was adjusted and then applied. First, common-source gather data were acquired to record TBM drilling noise (pilot signal and seismic waves); a processing approach (including normalization, crosscorrelation, wavefield separation, and migration) was used to image the major relevant geologic heterogeneities ahead of the excavation front. A synthetic study from a numerical model with a fault verified the feasibility of the modified TSWD method to identify and image geologic interfaces. Then, this method was applied to field data resulting from a TBM tunnel excavation project. The field test of the modified TSWD in the TBM tunnel revealed fractured zones, fault boundaries, and a preexcavated tunnel ahead, providing the required geologic information for TBM tunneling and preventing geologically-caused safety issues.
Bandwidth-insensitive extended centroid frequency-shift method for near-surfaceQestimation
Authors: Li Huijian , Liu Xu , Liu Bo , Greenhalgh Stewart , Al-Shuhail Abdullatif A. , Chen Yangkang
Published: November 2021

Seismic waves often are strongly attenuated in the near surface. The measurement and compensation for attenuation are crucial for high-resolution seismic imaging. The quality factor ([Formula: see text]), as a measure of attenuation, is usually estimated by frequency-based methods. We have extended the centroid frequency-shift (CFS) method for [Formula: see text] estimation to high loss media without the usual assumption of [Formula: see text]. The adaptability of this approach for an unknown source wavelet also is demonstrated. Skewness and kurtosis have been used for analyzing the spectral shape change during attenuated wave propagation. Synthetic data tests show a strong relationship between skewness and [Formula: see text] factor estimation accuracy for the conventional CFS method. Surprisingly, our extended CFS approach shows frequency band insensitivity and accuracy for strongly attenuating media. The relative insensitivity of the method to the selected or available frequency bandwidth is shown to be the theoretical basis for its good noise immunity. Finally, a layered medium [Formula: see text] inversion method is derived, which is appropriate to vertical seismic profile (VSP) surveying and is applied to a multioffset field VSP data set to obtain a reliable and stable internal [Formula: see text] value depth distribution.
Immunogenicity Risk Assessment for Multi-specific Therapeutics
Authors: Kroenke Mark A. , Milton Mark N. , Kumar Seema , Bame Eris , White Joleen T.
Published: November 2021

The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support the multi-specific therapeutic presented herein, the introduction focuses on known immunogenicity risk factors. The subsequent hypothetical case study applies these principles to a specific example HC-12, based loosely on anti-TNFα and anti-IL-17A bispecific molecules previously in development, structured as an example immunogenicity risk assessment for submission to health authorities. The risk of higher incidence and safety impact of anti-drug antibodies (ADA) due to large protein complexes is explored in the context of multi-specificity and multi-valency of the therapeutic in combination with the oligomeric forms of the targets.
Skeletal stem cell fate defects caused by Pdgfrb activating mutation
Authors: Kwon Hae Ryong , Kim Jang H. , Woods John P. , Olson Lorin E.
Published: November 2021

Autosomal dominant PDGFRβ gain-of-function mutations in mice and humans cause a spectrum of wasting and overgrowth disorders afflicting the skeleton and other connective tissues, but the cellular origin of these disorders remains unknown. We demonstrate that skeletal stem cells (SSCs) isolated from mice with a gain-of-function D849V point mutation in PDGFRβ exhibit colony formation defects that parallel the wasting or overgrowth phenotypes of the mice. Single-cell RNA transcriptomics with SSC-derived polyclonal colonies demonstrates alterations in osteogenic and chondrogenic precursors caused by PDGFRβD849V. Mutant cells undergo poor osteogenesis in vitro with increased expression of Sox9 and other chondrogenic markers. Mice with PDGFRβD849V exhibit osteopenia. Increased STAT5 phosphorylation and overexpression of Igf1 and Socs2 in PDGFRβD849V cells suggests that overgrowth in mice involves PDGFRβD849V activating the STAT5-IGF1 axis locally in the skeleton. Our study establishes that PDGFRβD849V causes osteopenic skeletal phenotypes that are associated with intrinsic changes in SSCs, promoting chondrogenesis over osteogenesis.
Zinc is an intracellular signal during sperm activation in Caenorhabditis elegans
Authors: Tan Chieh-Hsiang , Kornfeld Kerry
Published: November 2021

Sperm activation is a rapid and dramatic cell differentiation event that does not involve changes in transcription, and the signaling cascades that mediate this process have not been fully defined. zipt-7.1 encodes a zinc transporter, and zipt-7.1(lf) mutants display sperm-activation defects, leading to the hypothesis that zinc signaling mediates sperm activation in Caenorhabditis elegans. Here, we describe the development of a method for dynamic imaging of labile zinc during sperm activation using the zinc-specific fluorescence probe FluoZin-3 AM and time-lapse confocal imaging. Two phases of dynamic changes in labile zinc levels were observed during sperm activation. Forced zinc entry using the zinc ionophore pyrithione activated sperm in vitro, and it suppressed the defects of zipt-7.1(lf) mutants, indicating that high levels of cytosolic zinc are sufficient for sperm activation. We compared activation by zinc pyrithione to activation by extracellular zinc, the Na+/H+ antiporter monensin and the protease cocktail pronase in multiple mutant backgrounds. These results indicate that the protease pathway does not require zinc signaling, suggesting that zinc signaling is sufficient to activate sperm but is not always necessary.
Towards a shape-performance integrated digital twin for lumbar spine analysis
Authors: He Xiwang , Qiu Yiming , Lai Xiaonan , Li Zhonghai , Shu Liming , Sun Wei , Song Xueguan
Published: November 2021

Background: With significant advancement and demand for digital transformation, the digital twin has been gaining increasing attention as it is capable of establishing real-time mapping between physical space and virtual space. In this work, a shape-performance integrated digital twin solution is presented to predict the real-time biomechanics of the lumbar spine during human movement.

Methods: A finite element model (FEM) of the lumbar spine was firstly developed using computed tomography (CT) and constrained by the body movement which was calculated by the inverse kinematics algorithm. The Gaussian process regression was utilized to train the predicted results and create the digital twin of the lumbar spine in real-time. Finally, a three-dimensional virtual reality system was developed using Unity3D to display and record the real-time biomechanics performance of the lumbar spine during body movement.

Results: The evaluation results presented an agreement (R-squared > 0.8) between the real-time prediction from digital twin and offline FEM prediction.

Conclusions: This approach provides an effective method of real-time planning and warning in spine rehabilitation.
Ocimum basilicum (kemangi) intervention on powder and microencapsulated Spirulina platensis and its bioactive molecules
Authors: Yuliani Y , Riyadi Putut Har , Dewi Eko Nurcahya , Jaswir Irwandi , Agustini Tri Winarni
Published: November 2021

Background: Spirulina platensis contains several bioactive molecules such as phenol, flavonoid and phycocyanin pigments. This study unveils total phenol, flavonoid, antioxidant activity, phycocyanin content and evaluated encapsulation efficiency from Ocimum basilicum intervention on S. platensis. O. basilicum intervention aims to reduce unpleasant odors from S. platensis that will increase consumption and increase bioactive compounds.  

Methods: The intervention was carried out by soaking a S. platensis control sample (SP) in O. basilicum with a ratio of 1:4 (w/v) and it was then dried (DSB) and microencapsulated by freeze drying methods (MSB) using a combination of maltodextrin and gelatin. Total flavonoid and phenolic analysis with curve fitting analysis used a linear regression approach. Antioxidant activity of samples was analysed with the 2,2’-azino-bis-3-3thylbenzthiazoline-6-sulphonic acid (ABTS) method. Data were analysed using ANOVA at significance level (p < 0.05) followed by Tukey test models using SPSS v.22. 

Results: The result of this study indicated that O. basilicum intervention treatment (DSB) has the potential to increase bioactive compounds such as total phenol, antioxidant activity and phycocyanin, and flavonoid content. Intervention of O. basilicum on S. platensis (DSB) significantly increases total phenol by 49.5% and phycocyanin by 40.7%. This is due to the phenol and azulene compounds in O. basilicum which have a synergistic effect on phenol and phycocyanin in S. platensis. Microencapsulation using a maltodexrin and gelatin coating is effective in phycocyanin protection and antioxidant activity with an encapsulation efficiency value of 71.58% and 80.5%.  

Conclusion: The intervention of O. basilicum on S. platensis improved the total phenol and phycocyanin content and there is potential for a pharmaceutical product for a functional food and pharmaceutical product.
Nuevos modelos de negocios periodísticos. El caso de SUR ON+ y su incidencia en Twitter
Authors: López-Martín Álvaro , Molina Ruiz Santiago
Published: November 2021

En los últimos años diversas cabeceras están comenzando a implantar muros de pagos. Una de las últimas en sumarse a ello ha sido Sur. El análisis de los tuits referidos a SUR ON+ revela que este asunto tuvo una incidencia moderada entre los temas abordados. Aun así, la mayoría de los usuarios se muestran críticos con este modelo de negocio y se resisten a pagar por contenidos periodísticos.
Surgery Sequencing Coordination with Recovery Resource Constraints
Authors: Bai Miao , Storer Robert H. , Tonkay Gregory L.
Published: November 2021

Surgical practice administrators need to determine the sequence of surgeries and reserved operating room (OR) time for each surgery in the surgery scheduling process. Both decisions require coordination among multiple ORs and the recovery resource in the postanesthesia care unit (PACU) in a surgical suite. Although existing studies have addressed OR time reservation, surgery sequencing coordination is an open challenge in the stochastic surgical environment. In this paper, we propose an algorithmic solution to this problem based on stochastic optimization. The proposed methodology involves the development of a surrogate objective function that is highly correlated with the original one. The resulting surrogate model has network-structured subproblems after Lagrangian relaxation and decomposition, which makes it easier to solve than the impractically difficult original problem. We show that our proposed approach finds near-optimal solutions in small instances and outperforms benchmark methods by 13%–51% or equivalently an estimated saving of $760–$7,420 per day in surgical suites with 4–10 ORs. Our results illustrate a mechanism to alleviate congestion in the PACU. We also recommend that practice administrators prioritize sequencing coordination over the optimization of OR time reservation in an effort for performance improvement. Furthermore, we demonstrate how administrators should consider the impact of sequencing decisions when making strategic capacity adjustments for the PACU.

Summary of Contribution: Our work provides an algorithmic solution to an open question in the field of healthcare operations management. This solution approach involves formulating a surrogate optimization model and exploiting its decomposability and network-structure. In computational experiments, we quantitatively benchmark its performance and assess its benefits. Our numerical results provide unique managerial insights for healthcare leadership.
Pushing Notifications as Dynamic Information Design
Authors: Iyer Ganesh , Zhong Zemin (Zachary)
Published: November 2021

We study the dynamic information design problem of a firm seeking to influence consumer checking behavior by designing push notifications.
Tactical Target Date Funds
Authors: Gomes Francisco , Michaelides Alexander , Zhang Yuxin
Published: November 2021

We propose target date funds modified to exploit stock return predictability driven by the variance risk premium. The portfolio rule of these tactical target date funds (TTDFs) is extremely simplified relative to the optimal one, making it easy to implement and to communicate to investors. We show that saving for retirement in TTDFs generates economically large welfare gains, even after we introduce turnover restrictions and transaction costs, and after taking into account parameter uncertainty. This predictability also appears to be uncorrelated with individual household risk, suggesting that households are in a prime position to exploit it.

This paper was accepted by Tomasz Piskorski, finance.
Give Me Your Tired, Your Poor, Your High-Skilled Labor: H-1B Lottery Outcomes and Entrepreneurial Success
Authors: Dimmock Stephen G. , Huang Jiekun , Weisbenner Scott J.
Published: November 2021

We study how access to high-skill labor affects the outcomes of start-up firms. We obtain exogenous variation in firms’ ability to access skilled labor by using win rates in H-1B visa lotteries. Relative to other firms that also applied for H-1B visas, firms with higher lottery win rates are more likely to receive additional venture capital funding and to have a successful exit via an IPO or acquisition. H-1B visa lottery winners also subsequently receive more patents and patent citations. Overall, our results suggest that access to high-skill labor is a critical determinant of success for start-up firms.

This paper was accepted by Gustavo Manso, finance.