bluuebunny/crossref_metadata_2025 huggingface dataset:
From zero surgeries to candidates for exotic definite 4‐manifolds
Authors: Manolescu Ciprian , Piccirillo Lisa
Published: August 2023

One strategy for distinguishing smooth structures on closed 4‐manifolds is to produce a knot in that is slice in one smooth filling of but not slice in some homeomorphic smooth filling . In this paper, we explore how 0‐surgery homeomorphisms can be used to potentially construct exotic pairs of this form. To systematically generate a plethora of candidates for exotic pairs, we give a fully general construction of pairs of knots with the same zero surgeries. By computer experimentation, we find five topologically slice knots such that, if any of them were slice, we would obtain an exotic 4‐sphere. We also investigate the possibility of constructing exotic smooth structures on in a similar fashion.
Closing the Loop
Authors: Gibson Tom
Published: August 2023

While carbon footprint and cost reductions provide plenty of incentive for manufacturers to use recycled materials, another factor has come on the scene in recent years—a concept known as Extended Producer Responsibility (EPR). EPR incorporates all the environmental costs in the lifecycle of consumer products and packaging, and instead shifts the burden of waste management from consumers and government to manufacturers.
Sport Specialization’s Impact on Female Adolescent Athletes’ Lower-Extremity Neuromuscular Control: A Critically Appraised Topic
Authors: Reich Sierra , Hawkins Jeremy , Powell Alli , Reeder Michael
Published: August 2023

Clinical Scenario: Nearly 60 million youth ages 6–18 participate in athletics within the United States. Over the last 30 years, the outlook on youth sport participation has drastically changed, resulting in an increased emphasis on performance and college sport participation. These evolving expectations have created a sense of perfectionism, demanding more time and energy to be placed into a single sport, resulting in an increased prevalence of sport specialization, and consequently, an increased rate of injury. Clinical Question: What is the impact of sport specialization on lower-extremity neuromuscular control in female adolescent athletes? Summary of Key Findings: Four studies were included, all comparing movement efficiency and movement patterns among multisport and sport-specialized female adolescent athletes. Three studies showed that sport specialization is associated with lower-extremity biomechanical alterations that are indicative of altered levels of neuromuscular control, which can predispose an individual to an increased risk of injury. One study concluded that no differences in neuromuscular control exist when comparing sport-specialized to multisport adolescent female athletes. Clinical Bottom Line: Sport specialization has the potential to create negative alterations in a female adolescent athletes’ lower-extremity biomechanics, leading to the creation of altered levels of neuromuscular control and a possible increased risk for injury. Strength of Recommendation: Level B evidence exists to support the conclusion that sport specialization negatively affects a female adolescent athlete’s lower-extremity neuromuscular control.
Return to Sport and Clinical Outcomes Following Osteochondral Autograft Transplantation in Baseball Players and Gymnasts With Unstable Osteochondritis Dissecans: A Critically Appraised Topic
Authors: Myers Natalie L. , Kennedy Sean M. , Thorburn Luke D. , Conway John E. , Garrison J. Craig
Published: August 2023

Clinical Scenario: Osteochondritis dissecans (OCD) of the capitellum is a condition occurring at the elbow and often seen in both baseball players and gymnasts due to the repetitive loading of the radiocapitellar joint. Treatment options for OCD vary and are dependent on lesion presentation, elbow motion, and growth plate maturity. OCD lesions categorized as unstable can be treated with an osteochondral autograft transplantation surgery (OATS). Focused Clinical Question: In an adolescent population, what are the return to sport rates and clinical outcomes following OATS in baseball players and gymnasts with unstable OCD lesions? Summary of Key Findings: Three articles met the inclusion criteria for this appraisal, and all indicate an OATS procedure should be considered in the management of unstable OCD lesions. Return to play outcomes were favorable for both baseball players and gymnasts. Self-reported patient function and elbow extension all improved following an OATS. Clinical Bottom Line: An OATS procedure is a favorable option for the management of OCD lesions of the elbow in baseball players and gymnasts. Strength of Recommendation: There is level B evidence to support return to sport and clinical outcomes in baseball players and gymnasts following an OATS procedure. This score is directly related to the quality of evidence that currently exists on the topic.
Effect of Low-Load Blood Flow Restriction Training on Patients With Functional Ankle Instability: A Randomized Controlled Trial
Authors: Wen Ziliang , Zhu Jiang , Wu Xuelian , Zheng Bing , Zhao Li , Luo Xin , Wu Zonghui
Published: August 2023

Context: Decreased muscle strength and balance in patients with functional ankle instability (FAI) can be effectively improved by ankle strength training. Low-load blood flow restriction (LL-BFR) training increases muscle size and strength, but there is limited evidence from studies on muscle strength and balance in FAI patients. Objective: To study the effects of LL-BFR training versus high-load training (HLT) on muscle strength and balance in FAI patients. Design: Randomized controlled trial. Participants: Forty-six young adults with a history of FAI. Interventions: Participants in the LL-BFR and HLT groups performed 4 sets (30 × 15 × 15 × 15) of ankle training at 20% to 40% of the one-repetition maximum and 70% to 85% one-repetition maximum, respectively, twice a week for 6 weeks. Main Outcome Measure(s): Plantar flexion, dorsiflexion, inversion, and eversion muscle strength, and the Y-balance test scores were assessed at baseline and after 3 and 6 weeks; the thickness of the tibialis anterior, triceps surae, and peroneus longus muscles were assessed at baseline and after 6 weeks. Results: Inversion, eversion, dorsiflexion, and plantar flexion muscle strength; tibialis anterior, triceps surae, and peroneus longus thickness; and Y-balance test scores were significantly increased in the LL-BFR group after 3 and 6 weeks compared with baseline (P < .05), with no significant difference between the LL-BFR and HLT groups after 6 weeks (P > .05). However, at the end of 3 weeks, eversion muscle strength and Y-balance test scores were significantly higher in the LL-BFR group than in the HLT group (P < .05). Conclusions: Over 6 weeks, LL-BFR training was as effective as HLT in improving ankle muscle strength, muscle thickness, and balance in FAI patients, but LL-BFR training improved the ankle eversion muscle strength and dynamic balance more than HLT did in the early stages of the intervention. This finding will provide a new intervention strategy for the clinical rehabilitation of FAI patients.
Next-generation magnesium-ion batteries: The quasi-solid-state approach to multivalent metal ion storage
Authors: Leong Kee Wah , Pan Wending , Yi Xiaoping , Luo Shijing , Zhao Xiaolong , Zhang Yingguang , Wang Yifei , Mao Jianjun , Chen Yue , Xuan Jin , Wang Huizhi , Leung Dennis Y. C.
Published: August 2023

Mg-ion batteries offer a safe, low-cost, and high–energy density alternative to current Li-ion batteries. However, nonaqueous Mg-ion batteries struggle with poor ionic conductivity, while aqueous batteries face a narrow electrochemical window. Our group previously developed a water-in-salt battery with an operating voltage above 2 V yet still lower than its nonaqueous counterpart because of the dominance of proton over Mg-ion insertion in the cathode. We designed a quasi-solid-state magnesium-ion battery (QSMB) that confines the hydrogen bond network for true multivalent metal ion storage. The QSMB demonstrates an energy density of 264 W·hour kg
−1
, nearly five times higher than aqueous Mg-ion batteries and a voltage plateau (2.6 to 2.0 V), outperforming other Mg-ion batteries. In addition, it retains 90% of its capacity after 900 cycles at subzero temperatures (−22°C). The QSMB leverages the advantages of aqueous and nonaqueous systems, offering an innovative approach to designing high-performing Mg-ion batteries and other multivalent metal ion batteries.
Co-condensation with photoexcited cryptochromes facilitates MAC3A to positively control hypocotyl growth in
Arabidopsis
Authors: Jiang Bochen , Zhong Zhenhui , Su Jun , Zhu Tengfei , Yueh Timothy , Bragasin Jielena , Bu Victoria , Zhou Charles , Lin Chentao , Wang Xu
Published: August 2023

Cryptochromes (CRYs) are blue light receptors that mediate plant photoresponses through regulating gene expressions. We recently reported that
Arabidopsis
CRY2 could form light-elicited liquid condensates to control RNA methylation. However, whether CRY2 condensation is involved in other gene expression–regulatory processes remains unclear. Here, we show that MOS4-associated complex subunits 3A and 3B (MAC3A/3B) are CRY-interacting proteins and assembled into nuclear CRY condensates.
mac3a3b
double mutants exhibit hypersensitive photoinhibition of hypocotyl elongation, suggesting that MAC3A/3B positively control hypocotyl growth. We demonstrate the noncanonical activity of MAC3A as a DNA binding protein that modulates transcription. Genome-wide mapping of MAC3A-binding sites reveals that blue light enhances the association of MAC3A with its DNA targets, which requires CRYs. Further evidence indicates that MAC3A and ELONGATED HYPOCOTYL 5 (HY5) occupy overlapping genomic regions and compete for the same targets. These results argue that photocondensation of CRYs fine-tunes light-responsive hypocotyl growth by balancing the opposed effects of HY5 and MAC3A.
A gut-restricted glutamate carboxypeptidase II inhibitor reduces monocytic inflammation and improves preclinical colitis
Authors: Peters Diane E. , Norris Lauren D. , Tenora Lukáš , Šnajdr Ivan , Ponti András K. , Zhu Xiaolei , Sakamoto Shinji , Veeravalli Vijayabhaskar , Pradhan Manisha , Alt Jesse , Thomas Ajit G. , Majer Pavel , Rais Rana , McDonald Christine , Slusher Barbara S.
Published: August 2023

There is an urgent need to develop therapeutics for inflammatory bowel disease (IBD) because up to 40% of patients with moderate-to-severe IBD are not adequately controlled with existing drugs. Glutamate carboxypeptidase II (GCPII) has emerged as a promising therapeutic target. This enzyme is minimally expressed in normal ileum and colon, but it is markedly up-regulated in biopsies from patients with IBD and preclinical colitis models. Here, we generated a class of GCPII inhibitors designed to be gut-restricted for oral administration, and we interrogated efficacy and mechanism using in vitro and in vivo models. The lead inhibitor, (
S
)-IBD3540, was potent (half maximal inhibitory concentration = 4 nanomolar), selective, gut-restricted (AUC
colon/plasma
> 50 in mice with colitis), and efficacious in acute and chronic rodent colitis models. In dextran sulfate sodium–induced colitis, oral (
S
)-IBD3540 inhibited >75% of colon GCPII activity, dose-dependently improved gross and histologic disease, and markedly attenuated monocytic inflammation. In spontaneous colitis in interleukin-10 (IL-10) knockout mice, once-daily oral (
S
)-IBD3540 initiated after disease onset improved disease, normalized colon histology, and attenuated inflammation as evidenced by reduced fecal lipocalin 2 and colon pro-inflammatory cytokines/chemokines, including tumor necrosis factor–α and IL-17. Using primary human colon epithelial air-liquid interface monolayers to interrogate the mechanism, we further found that (
S
)-IBD3540 protected against submersion-induced oxidative stress injury by decreasing barrier permeability, normalizing tight junction protein expression, and reducing procaspase-3 activation. Together, this work demonstrated that local inhibition of dysregulated gastrointestinal GCPII using the gut-restricted, orally active, small-molecule (
S
)-IBD3540 is a promising approach for IBD treatment.
Supplemental Material: Construction and Modification of Debris-Flow Alluvial Fans as Captured in the Geomorphic and Sedimentary Record: Examples from the Western Sangre de Cristo Mountains, South-Central Colorado
Authors: Nicovich Sylvia
Published: August 2023

Plate 1: Surficial Geologic Map of Alluvial Fans and Related Deposits along the Northern Sangre de Cristo Range Front, South-Central Colorado, USA 
Experience of reassessingFBN1variants of uncertain significance by gene-specific guidelines
Authors: Yoon Eungjun , Lee Jong Kwon , Park Taek Kyu , Chang Sung-A , Huh June , Kim Jong-Won , Kim Duk-Kyung , Jang Ja-Hyun
Published: August 2023

Background

Despite the 2015 American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) guideline, many variants ofFBN1gene remain inconclusive. In line with publication of theFBN1-specific variant interpretation guideline by ClinGen in 2022, we reassessed variants of uncertain significance (VUS) inFBN1gene found in our institution.

Methods

VUS found in the course ofFBN1sequencing between December 2015 and April 2022 were reassessed based onFBN1-specific variant interpretation guideline, review of updated literatures and additional genetic tests including family study and/or RNA study if available.

Results

Out of 695 patients who underwentFBN1sequencing, 61 VUS were found in 69 patients. Among them, 38 VUS in 43 patients (62.3%) were reclassified as pathogenic and likely pathogenic variant ((L)PV), including 20 novel (L)PV. Major causes of reclassification were: (1) gene-specific modification of ACMG/AMP criteria, (2) updated literatures and (3) additional genetic tests. The most important evidence for reclassification was clarification of critical amino acid residues.

Conclusions

After reassessingFBN1variants according toFBN1-specific guideline and up-to-date database, a significant number of VUS was reclassified. Clinical laboratories are encouraged to perform variant reassessment at regular intervals or when there is a major change in the principle of variant interpretation.
A preliminary study on the effect of loaded and unloaded exercise on N-propeptide of type II collagen and serum cartilage oligomeric matrix protein activity of articular cartilage in healthy young adults
Authors: de Vasconcelos Bruna Mavignier , Peeler Jason D. , Scribbans Trisha , Cornish Stephen M.
Published: August 2023

The serum concentration of cartilage oligomeric matrix protein (sCOMP) is considered a mechanosensitive biomarker of articular cartilage turnover, and N-propeptide of type II collagen (PIIANP), a proposed biomarker of type II collagen synthesis. Few studies have investigated the anabolic and turnover response of articular cartilage in response to acute changes in body mass during exercise. Using a repeated measure cross-over design, 15 healthy adults (age 18–30 years) performed three 30 min bouts of treadmill walking exercise under three loading conditions: (1) control (no alteration to body mass); (2) loaded (12% increase in body mass using a weighted vest); and (3) unloaded (12% decrease in body mass using lower body positive pressure). Venous blood was collected before, immediately after, and 15 and 30 min after exercise to investigate cartilage turnover (sCOMP) and anabolism (PIIANP). A main time effect ( p ≤ 0.05) revealed that sCOMP levels were significantly greater post-exercise (for all three body loading conditions) as compared to before exercise, 15 and 30 min post-exercise. There was a significant condition × time interaction ( p ≤ 0.05) for PIIANP, indicating that in the loaded condition, PIIANP concentrations at 15 min post-exercise were 13.8% greater than immediately following exercise, and 12.9% greater than before exercise. In summary, sCOMP concentration was acutely increased with all three loading conditions. However, PIIANP increased only after exercise in the loaded condition, suggesting an acute anabolic effect on articular cartilage. NCT05925244.
Impact of concrete masonry unit geometry on masonry assemblage strength
Authors: Chhetri Nitesh , Feldman Lisa R.
Published: August 2023

An experimental investigation of 126 masonry prisms was conducted to assess the influence of concrete masonry unit web height on structural response. All prisms had the same overall geometry, were either grouted or left hollow, and included regular stretcher units with full-height webs, knock-out units with remaining web height conforming to typical Canadian practice, or knock-out units with remaining web height resulting in a calculated normalized web area approaching the minimum permissible in accordance with U.S. standard ASTM C90. Cracks in hollow prisms shifted from the centre of the exterior web face for those constructed with regular stretcher units to the web–face shell interface as the remaining web height decreased. The stability of the grout columns in grouted prisms reduced stress concentrations at the web–face shell interface and the effects of increased restraint with reduced height-to-thickness ratio.
Precision CMB constraints on eV-scale bosons coupled to neutrinos
Authors: Sandner Stefan , Escudero Miguel , Witte Samuel J.
Published: August 2023

The cosmic microwave background (CMB) has proven to be an invaluable tool for studying the properties and interactions of neutrinos, providing insight not only into the sum of neutrino masses but also the free streaming nature of neutrinos prior to recombination. The CMB is a particularly powerful probe of new eV-scale bosons interacting with neutrinos, as these particles can thermalize with neutrinos via the inverse decay process, $$\nu \bar{\nu } \rightarrow X$$

ν

ν

¯

→
X

, and suppress neutrino free streaming near recombination – even for couplings as small as $$\lambda _{\nu } \sim {\mathcal {O}}(10^{-13})$$

λ
ν

∼
O

(

10

-
13

)

. Here, we revisit CMB constraints on such bosons, improving upon a number of approximations previously adopted in the literature and generalizing the constraints to a broader class of models. This includes scenarios in which the boson is either spin-0 or spin-1, the number of interacting neutrinos is either $$N_{\textrm{int}} = 1,2 $$

N
int

=
1
,
2

or 3, and the case in which a primordial abundance of the species is present. We apply these bounds to well-motivated models, such as the singlet majoron model or a light $$U(1)_{L_{\mu }-L_{\tau }}$$

U

(
1
)

L
μ

-

L
τ

gauge boson, and find that they represent the leading constraints for masses $$m_X\sim 1\, {\textrm{eV}}$$

m
X

∼
1

eV

. Finally, we revisit the extent to which neutrino-philic bosons can ameliorate the Hubble tension, and find that recent improvements in the understanding of how such bosons damp neutrino free streaming reduces the previously found success of this proposal.
Random Testing and Evolutionary Testing for Fuzzing GraphQL APIs
Authors: Belhadi Asma , Zhang Man , Arcuri Andrea
Published: August 2023

The Graph Query Language (GraphQL) is a powerful language for application programming interface (API) manipulation in web services. It has been recently introduced as an alternative solution for addressing the limitations of RESTful APIs. This article introduces an automated solution for GraphQL API testing. We present a full framework for automated API testing, from the schema extraction to test case generation. In addition, we consider two kinds of testing: white-box and black-box testing. The white-box testing is performed when the source code of the GraphQL API is available. Our approach is based on evolutionary search. Test cases are evolved to intelligently explore the solution space while maximizing code coverage and fault-finding criteria. The black-box testing does not require access to the source code of the GraphQL API. It is therefore of more general applicability, albeit it has worse performance. In this context, we use a random search to generate GraphQL data. The proposed framework is implemented and integrated into the open source
EvoMaster
tool. With enabled white-box heuristics (i.e., white-box mode), experiments on 7 open source GraphQL APIs and three search algorithms show statistically significant improvement of the evolutionary approach compared to the baseline random search. In addition, experiments on 31 online GraphQL APIs reveal the ability of the black-box mode to detect real faults.
Nocturnal Hypoventilation in the Patients Submitted to Thoracic Surgery
Authors: Majchrzak Maciej , Daroszewski Cyryl , Błasiak Piotr , Rzechonek Adam , Piesiak Paweł , Kosacka Monika , Brzecka Anna
Published: August 2023

Introduction. Nocturnal hypoventilation may occur due to obesity, concomitant chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and/or the use of narcotic analgesics. The aim of the study was to evaluate the risk and severity of nocturnal hypoventilation as assessed by transcutaneous continuous capnography in the patients submitted to thoracic surgery. Materials and Methods. The material of the study consisted of 45 obese (BMI 34.8 ± 3.7 kg/m2) and 23 nonobese (25.5 ± 3.6 kg/m2) patients, who underwent thoracic surgery because of malignant (57 patients) and nonmalignant tumors. All the patients received routine analgesic treatment after surgery including intravenous morphine sulfate. Overnight transcutaneous measurements of CO2 partial pressure (tcpCO2) were performed before and after surgery in search of nocturnal hypoventilation, i.e., the periods lasting at least 10 minutes with tcpCO2 above 55 mmHg. Results. Nocturnal hypoventilation during the first night after thoracic surgery was detected in 10 patients (15%), all obese, three of them with COPD, four with high suspicion of moderate-to-severe OSA syndrome, and one with chronic daytime hypercapnia. In the patients with nocturnal hypoventilation, the mean tcpCO2 was 53.4 ± 6.1 mmHg, maximal tcpCO2 was 59.9 ± 8.4 mmHg, and minimal tcpCO2 was 46.4 ± 6.7 mmHg during the first night after surgery. In these patients, there were higher values of minimal, mean, and maximal tcpCO2 in the preoperative period. Nocturnal hypoventilation in the postoperative period did not influence the duration of hospitalization. Among 12 patients with primary lung cancer who died during the first two years of observation, there were 11 patients without nocturnal hypoventilation in the early postoperative period. Conclusion. Nocturnal hypoventilation may occur in the patients after thoracic surgery, especially in obese patients with bronchial obstruction, obstructive sleep apnea, or chronic daytime hypercapnia, and does not influence the duration of hospitalization.
Gastrointestinal Parasites of the Ethiopian Rock Hyrax (Procavia capensis, Pallas, 1766) in the North East Region of Ghana
Authors: Bimi Langbong , Tetteh Ato Kwamena , Oduro Daniel , Anto Francis
Published: August 2023

Wildlife may serve as potential reservoirs and intermediate or accidental hosts of zoonotic pathogens due to their interactions with human beings. For the first time in Ghana, we report extempore the gastrointestinal parasites of three Ethiopian rock hyraxes captured in September 2021. Forty adult parasites (21 nematodes and 19 tapeworms) were recovered from the gastrointestinal tracts of these three game hyraxes (Procavia capensis, Pallas, 1766) from the hills of Bimbagu (near the Gambaga Scarp) in the North East Region of Ghana. Adult worms comprising 16 tapeworms and 24 nematodes were identified. The intestinal faecal examination detected ova of Trichuris spp., tapeworms, and hookworms. The results are presented alongside the results of the molecular determination of the worm identities. Since wildlife has been identified as an important source of emerging human pathogens, including helminth parasites, there is an urgent need for sufficient literature on wildlife parasites in Ghana. As the rock hyrax is hunted for its meat, there is a potential risk of transmitting these identified helminths and other zoonotic pathogens to humans, especially involving people who handle the carcasses as the transmission is faecal-oral. A more precarious situation may arise when the eggs of cestodes are ingested by handlers of these carcasses and could result in cysticercosis/neuro-cysticercosis when these eggs cross the blood-brain barrier in the person.
Experiences of Health Service Access and Use for People Living with Parkinson’s Disease in Ireland: A National Survey
Authors: O’ Shea Emma , Rukundo Aphie , Bennett Kathleen , Foley Geraldine , Wilkinson Tony , Timmons Suzanne
Published: August 2023

Background. Despite the growing prevalence of Parkinson’s disease (PD) and the need to plan for future health service provision, little is known in the Irish context about PD patients’ experiences of service access/use. Methods. A cross-sectional survey, with multiple formats, i.e., online, pen-and-paper, and telephone. Data were collected from May 2020 to July 2021 using a multipronged recruitment strategy. The survey was completed by people with PD alone or with the support of a carer/support person. Results. A total of 1402 responses were included. Over half (53%) were male. Approx. 10% were diagnosed with young-onset PD. A minority (6%) reported attending only their GP to manage their PD, with the rest attending a generic or specialist outpatient clinic. Almost 1-in-5 reported it took more than 12 months to obtain the diagnosis. Most were diagnosed by neurologists (84%), followed by GPs (8%) and geriatricians (7%); 1% indicated “other.” Of those diagnosed privately, 37% of these patients subsequently switched to the public system for ongoing management. The majority (97%) reported currently taking PD medications, but just 52% believed these were working effectively. Access to the range of health and social care professionals, including PD nurse specialists and clinical therapies is universally poor. Conclusions. A number of significant gaps in PD care are discussed, which require urgent attention. A reconfigured model of PD care is necessary to accommodate the growing need for specialist, integrated care at the population level. Specifically, more PD nurse specialists are needed within the public health system.
Isolated Fallopian Tube Torsion with Necrotic Hemorrhagic Cyst in an 11-Year-Old Girl Diagnosed by Laparoscopy
Authors: Arias Rivera Atl Simon , Zamora Duarte Luis Miguel , Shuchleib Chaba Samuel , Chousleb Kalach Alberto , Jalak Cababie Marcos , Shuchleib Cung Ariel
Published: August 2023

Isolated fallopian tube torsion (IFTT) is a rare pathology that causes acute abdomen in women, it is even less common in pediatric patients. We present a case of an 11-year-old girl who presented with abdominal pain 24 hours of evolution, the diagnosis could not be specified with cabinet methods, so the definitive diagnosis was made using a diagnostic laparoscopy. A necrotic hemorrhagic tubal cyst was found. A left salpingectomy had to be performed due to necrosis. Early diagnosis can have a positive impact on the fertility of these patients.
Supplementary Information from Heterogeneity of Circulating Tumor Cell–Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response
Authors: Kanwar Nisha , Balde Zaldy , Nair Ranju , Dawe Melanie , Chen Shiyi , Maganti Manjula , Atenafu Eshetu G. , Manolescu Sabrina , Wei Carrie , Mao Amanda , Fu Fred , Wang Dan , Cheung Alison , Yerofeyeva Yulia , Peters Rachel , Liu Kela , Desmedt Christine , Sotiriou Christos , Szekely Borbala , Kulka Janina , McKee Trevor D. , Hirano Naoto , Bartlett John M.S. , Yaffe Martin J. , Bedard Philippe L. , McCready David , Done Susan J.
Published: August 2023

Includes Supplemental Figure S1 and Supplemental Tables S1-S7
Supplementary File from Heterogeneity of Circulating Tumor Cell–Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response
Authors: Kanwar Nisha , Balde Zaldy , Nair Ranju , Dawe Melanie , Chen Shiyi , Maganti Manjula , Atenafu Eshetu G. , Manolescu Sabrina , Wei Carrie , Mao Amanda , Fu Fred , Wang Dan , Cheung Alison , Yerofeyeva Yulia , Peters Rachel , Liu Kela , Desmedt Christine , Sotiriou Christos , Szekely Borbala , Kulka Janina , McKee Trevor D. , Hirano Naoto , Bartlett John M.S. , Yaffe Martin J. , Bedard Philippe L. , McCready David , Done Susan J.
Published: August 2023

Raw cell counts of FISH gene probes for (1) primary breast tumors, (2) metastatic sites, (3) pre- and post-treatment [Hungarian sample], and (4) TNBC cases.
Supplementary Table 1 from Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study
Authors: Chowdhury-Paulino Ilkania M. , Hart Jaime E. , James Peter , Iyer Hari S. , Wilt Grete E. , Booker Benjamin D. , Nethery Rachel C. , Laden Francine , Mucci Lorelei A. , Markt Sarah C.
Published: August 2023

Supplementary Table 1. Hazard ratios and 95% confidence intervals for the association between cumulative average outdoor light at night (LAN) and lethal prostate cancer risk in HPFS (1986-2016)
Supplementary Figure 1 from Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study
Authors: Chowdhury-Paulino Ilkania M. , Hart Jaime E. , James Peter , Iyer Hari S. , Wilt Grete E. , Booker Benjamin D. , Nethery Rachel C. , Laden Francine , Mucci Lorelei A. , Markt Sarah C.
Published: August 2023

Supplementary Figure 1. Cubic splines to check for nonlinearity (A) Spline for total prostate cancer; (B) Spline for fatal prostate cancer
Supplementary Table S2 from Racial and Ethnic Variation in Diagnostic Mammography Performance among Women Reporting a Breast Lump
Authors: Nyante Sarah J. , Abraham Linn , Aiello Bowles Erin J. , Lee Christoph I. , Kerlikowske Karla , Miglioretti Diana L. , Sprague Brian L. , Henderson Louise M.
Published: August 2023

Ultrasound/MRI use by age and racial/ethnic group
Supplemental Table 6 from Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts
Authors: Kotsopoulos Joanne , Hathaway Cassandra A. , Narod Steven A. , Teras Lauren R. , Patel Alpa V. , Hu Chunling , Yadav Siddhartha , Couch Fergus J. , Tworoger Shelley S.
Published: August 2023

Supplemental Table 6: Total number of mutations across 12 cancer predisposing genes among ovarian cancer cases and controls in the NHS, NHSII, and CPSII
Supplemental Table 4 from Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts
Authors: Kotsopoulos Joanne , Hathaway Cassandra A. , Narod Steven A. , Teras Lauren R. , Patel Alpa V. , Hu Chunling , Yadav Siddhartha , Couch Fergus J. , Tworoger Shelley S.
Published: August 2023

Supplemental Table 4: Mutation frequencies in high grade serous, endometroid, or poorly differentiated ovarian cancer cases and controls and risk of ovarian cancer in the NHS, NHSII, and CPSII
Supplemental Table 1 from Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts
Authors: Kotsopoulos Joanne , Hathaway Cassandra A. , Narod Steven A. , Teras Lauren R. , Patel Alpa V. , Hu Chunling , Yadav Siddhartha , Couch Fergus J. , Tworoger Shelley S.
Published: August 2023

Supplemental Table 1: Characteristics from cohort (2004 NHS; 2007 NHSII, and baseline in CPSII) compared to women with blood or cheek sample
Supplemental Figure 2 from Germline Mutations in 12 Genes and Risk of Ovarian Cancer in Three Population-Based Cohorts
Authors: Kotsopoulos Joanne , Hathaway Cassandra A. , Narod Steven A. , Teras Lauren R. , Patel Alpa V. , Hu Chunling , Yadav Siddhartha , Couch Fergus J. , Tworoger Shelley S.
Published: August 2023

Supplemental Figure 2: Kaplan-Meier survival curves for ovarian cancer-specific mortality among cases with Type II tumors (high/unknown grade serous, poorly differentiated, or high grade endometrioid) for A) BRCA1 mutation carriers, B) BRCA2 mutation carriers (solid black lines). Grey lines are women with no mutation in any of the measured high-penetrance genes. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox Proportional hazard models and were adjusted for age at diagnosis (continuous), year of ovarian cancer diagnosis (continuous), and stage (0, I, II, III, IV, Unknown)
Data from Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study
Authors: Chowdhury-Paulino Ilkania M. , Hart Jaime E. , James Peter , Iyer Hari S. , Wilt Grete E. , Booker Benjamin D. , Nethery Rachel C. , Laden Francine , Mucci Lorelei A. , Markt Sarah C.
Published: August 2023

AbstractBackground:
Circadian disruption is a potential risk factor for advanced prostate cancer, and light at night (LAN) exposure may disrupt circadian rhythms. We evaluated whether outdoor LAN increases the risk of prostate cancer.
Methods:
We prospectively followed 49,148 participants in the Health Professionals Follow-up Study from 1986 through 2016. We estimated baseline and cumulative time-varying outdoor LAN with ∼1 km2 resolution using data from the US Defense Meteorological Satellite Program's Operational Linescan System, which was assigned to participants’ geocoded addresses. Participants reside in all 50 U.S. states and reported a work or home address. We used multivariable Cox models to estimate HRs and 95% confidence intervals (CI) for the association between outdoor LAN and risk of overall (7,175 cases) and fatal (915 cases) prostate cancer adjusting for individual and contextual factors.
Results:
There was no association between the interquartile range increase in cumulative LAN and total (HR, 1.02; 95% CI, 0.98–1.06) or fatal (HR, 1.05; 95% CI, 0.96–1.15) prostate cancer in adjusted models. However, there was a positive association between baseline LAN and total prostate cancer among non-movers (HR, 1.06; 95% CI, 1.00–1.14) including among highly screened participants (HR, 1.11; 95% CI, 1.01–1.23).
Conclusions:
There was a suggestive positive association between baseline outdoor LAN and total prostate cancer. Additional studies with different measures of outdoor LAN and in more diverse populations are necessary.
Impact:
To our knowledge, this is the first longitudinal cohort study exploring the relationship between outdoor LAN and prostate cancer.
Germline Genetic Variants Associated with Somatic TMPRSS2:ERG Fusion Status in Prostate Cancer: A Genome-Wide Association Study
Authors: Ma Chaoran , Wang Xiaoyu , Dai James Y. , Turman Constance , Kraft Peter , Stopsack Konrad H. , Loda Massimo , Pettersson Andreas , Mucci Lorelei A. , Stanford Janet L. , Penney Kathryn L.
Published: August 2023

Background:

The prostate cancer subtype defined by the presence of TMPRSS2:ERG has been shown to be molecularly and epidemiologically distinct. However, few studies have investigated germline genetic variants associating with TMPRSS2:ERG fusion status.

Methods:

We performed a genome-wide association study with 396 TMPRSS2:ERG(+) cases, 390 TMPRSS2:ERG(−) cases, and 2,386 cancer-free controls from the Physicians’ Health Study (PHS), the Health Professionals Follow-up Study (HPFS), and a Seattle-based Fred Hutchinson (FH) Cancer Center Prostate Cancer Study. We applied logistic regression models to test the associations between ∼5 million SNPs with TMPRSS2:ERG fusion status accounting for population stratification.

Results:

We did not identify genome-wide significant variants comparing the TMPRSS2:ERG(+) to the TMPRSS2:ERG(−) prostate cancer cases in the meta-analysis. When comparing TMPRSS2:ERG(+) prostate cancer cases with controls without prostate cancer, 10 genome-wide significant SNPs on chromosome 17q24.3 were observed in the meta-analysis. When comparing TMPRSS2:ERG(−) prostate cancer cases with controls without prostate cancer, two SNPs on chromosome 8q24.21 in the meta-analysis reached genome-wide significance.

Conclusions:

We observed SNPs at several known prostate cancer risk loci (17q24.3, 1q32.1, and 8q24.21) that were differentially and exclusively associated with the risk of developing prostate tumors either with or without the gene fusion.

Impact:

Our findings suggest that tumors with the TMPRSS2:ERG fusion exhibit a different germline genetic etiology compared with fusion negative cases.
Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival
Authors: Babic Ana , Wang Qiao-Li , Lee Alice A. , Yuan Chen , Rifai Nader , Luo Juhua , Tabung Fred K. , Shadyab Aladdin H. , Wactawski-Wende Jean , Saquib Nazmus , Kim Jihye , Kraft Peter , Sesso Howard D. , Buring Julie E. , Giovannucci Edward L. , Manson JoAnn E. , Stampfer Meir J. , Ng Kimmie , Fuchs Charles S. , Wolpin Brian M.
Published: August 2023

Background:

Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.

Methods:

Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).

Results:

Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15–2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46–1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51–0.84, and HR, 1.33; 95% CI, 1.12–1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25–1.90), 0.72 (95% CI, 0.59–0.88), and 0.70 (95% CI, 0.56–0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23–0.66; Pinteraction = 0.0002).

Conclusions:

High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.

Impact:

Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
Efficacy and Safety of Stereotactic Body Radiotherapy Combined with Camrelizumab and Apatinib in Patients with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
Authors: Hu Yue , Zhou Min , Tang Jing , Li Shuang , Liu Hongli , Hu Jianli , Ma Hong , Liu Junli , Qin Tingting , Yu Xiongjie , Chen Yongshun , Peng Jin , Zou Yanmei , Zhang Tao , Xue Jun
Published: August 2023

Purpose:

This study aimed to evaluate the efficacy and safety of camrelizumab plus apatinib with or without stereotactic body radiotherapy (SBRT) as first-line therapy for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Patients and Methods:

This is a multicenter, open-label, noncomparative, randomized trial that recruited patients with HCC with type II/III/IV PVTT, who had not previously received systemic therapy. Patients were randomly assigned (2:1) to receive camrelizumab (200 mg, every 3 weeks) and apatinib (250 mg, every day) with or without SBRT [95% planning target volume (PTV), 36–40 Gy/6–8 Gy]. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response, time to progression, and safety.

Results:

Sixty patients were enrolled and randomly assigned to two prospective cohorts. Median OS were 12.7 months [95% confidence interval (CI), 10.2–not available (NA)] and 8.6 months (95% CI, 5.6–NA), and median PFS were 4.6 months (95% CI, 3.3–7.0) and 2.5 months (95% CI, 2.0–7.6) for the SBRT and non-SBRT cohorts, respectively. The ORR and DCR were 47.5% and 72.5% in the SBRT cohort, and 20.0% and 40.0% in the non-SBRT cohort. The most common treatment-related adverse events of any grade were hypertension (55.0%), hand-foot syndrome (51.7%), and leukopenia (50.0%). Grade ≥ 3 was reported in 13 (21.7%) patients.

Conclusions:

First-line treatment with camrelizumab–apatinib combined with or without SBRT showed clinical benefits in patients with HCC with PVTT, with an acceptable safety profile. Thus, these combination regimens may be potential options for such patients.
Supplementary Figure 1 from A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells
Authors: Reddy Vidyavathi , Hwang Clara , Reddy G. Prem-Veer , Kim Sahn-Ho
Published: August 2023

Supplementary Figure 1
Supplementary Figure 1 Legend from A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells
Authors: Reddy Vidyavathi , Hwang Clara , Reddy G. Prem-Veer , Kim Sahn-Ho
Published: August 2023

Lack of AR expression is not the cause for telomere DNA damage in PC-3 cells.
Table S8 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Antibody dilutions for primary and secondary antibodies used
Table S6 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Sequences of guide RNAs used to generate genetic knockouts
Table S4 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Z-transformed difference scores for each cell line as calculated from beta scores
Supplementary Figure Legends 1-7 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

S1. BYL719 and DMSO beta scores
S2. Ribbon plots of non-gastric cancer cell lines included in screen.
S3. Dasatinib renders AGS cells hyper-sensitive to BYL719
S4. Loss of BCL-XL induces cell death in BYL719 treated MKN1
S5. BCL-XL inhibitor A-1331852 is the only inhibitor capable of increasing BYL719-induced cell death and inhibiting cell growth.
S6. CBFB binding co-factor RUNX1 is down-regulated at protein and mRNA level in BYL719 resistant clones.
S7. Pan-PIM inhibition or PIM1 KO re-sensitizes CBFB KO and resistant clones to BYL719.
Figure S7 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Figure S7 shows loss of PIM1 re-sensitizes resistant cells to BYL719
Figure S5 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Figure S5 shows BH3 mimetics and MCL1 modifiers in combination with BYL719
Figure S3 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Figure S3 shows that Dasatinib renders cells hyper-sensitive to BYL719
Figure S2 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: August 2023

Figure S2 shows ribbon plots generated for non-gastric cancer cell lines included in the screen
Data from A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells
Authors: Reddy Vidyavathi , Hwang Clara , Reddy G. Prem-Veer , Kim Sahn-Ho
Published: August 2023

Abstract
Prostate-specific membrane antigen (PSMA) expression increases with prostate cancer grade and progression; however, the role of PSMA in prostate cancer progression remains poorly understood. Telomere stability is essential for the survival and genome stability of cancer cells. We found massive telomere DNA damage in PSMA-negative prostate cancer cells (PC-3 and DU145) compared with PSMA-positive prostate cancer (LNCaP) cells. The ectopic expression of PSMA suppressed telomere DNA damage in PC3 cells. PSMA inhibitor, 2-PMPA, and PSMA knockdown induced telomere DNA damage in PSMA-positive LNCaP cells but not in PSMA-negative PC-3 cells, suggesting that PSMA plays a critical role in telomere stability in prostate cancer cells. In addition, we observed that inhibition of PSMA or inhibition of glutamate receptor, which mediates PSMA-dependent activation of AKT, suppressed AKT phosphorylation, and caused telomere DNA damage. Furthermore, 2-PMPA-induced telomere DNA damage in LNCaP cells was associated with telomere aberrations, such as telomere–telomere fusions, sister–chromatid telomere fusions, and telomere breakages. AKT is reported to promote cell growth by stabilizing telomere association with telomere-binding proteins TRF1 and TPP1. We observed that TRF1 and TPP1 transfection of LNCaP cells attenuated the inhibitory effect of 2-PMPA on cell growth and telomere DNA damage. Together, these observations indicate that PSMA role in maintaining telomere stability in prostate cancer cells is mediated by AKT. Thus, these studies reveal an important role of PSMA in maintaining telomere stability that can promote cell survival and, thereby, prostate cancer progression.
Implications:
Role of PSMA in telomere stability suggests a strong correlation between PSMA expression and prostate cancer progression.
Supplementary Video S5 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Dashzeveg Nurmaa K. , Jia Yuzhi , Zhang Youbin , Gerratana Lorenzo , Patel Priyam , Shajahan Asif , Dandar Tsogbadrakh , Ramos Erika K. , Almubarak Hannah F. , Adorno-Cruz Valery , Taftaf Rokana , Schuster Emma J. , Scholten David , Sokolowski Michael T. , Reduzzi Carolina , El-Shennawy Lamiaa , Hoffmann Andrew D. , Manai Maroua , Zhang Qiang , D'Amico Paolo , Azadi Parastoo , Colley Karen J. , Platanias Leonidas C. , Shah Ami N. , Gradishar William J. , Cristofanilli Massimo , Muller William A. , Cobb Brian A. , Liu Huiping
Published: August 2023

Supplementary Video S5 shows the clustering video of ST6WT cells presented in Fig.2B.
Supplementary Video S4 from Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer
Authors: Dashzeveg Nurmaa K. , Jia Yuzhi , Zhang Youbin , Gerratana Lorenzo , Patel Priyam , Shajahan Asif , Dandar Tsogbadrakh , Ramos Erika K. , Almubarak Hannah F. , Adorno-Cruz Valery , Taftaf Rokana , Schuster Emma J. , Scholten David , Sokolowski Michael T. , Reduzzi Carolina , El-Shennawy Lamiaa , Hoffmann Andrew D. , Manai Maroua , Zhang Qiang , D'Amico Paolo , Azadi Parastoo , Colley Karen J. , Platanias Leonidas C. , Shah Ami N. , Gradishar William J. , Cristofanilli Massimo , Muller William A. , Cobb Brian A. , Liu Huiping
Published: August 2023

Supplementary Video S4 shows the clustering video of ST6OE cells presented in Fig.2B