bluuebunny/crossref_metadata_2025 huggingface dataset:
Did the PNR judgment address the core issues raised by mass surveillance?
Authors: Korff Douwe
Published: January 2024

This article looks at three main issues raised by the PNR scheme: (i) the base‐rate fallacy and its effect on false positives; (ii) built‐in biases; and (iii) opacity and unchallengeability of the decisions generated, and at whether the Court has properly addressed them. It concludes that the AG and the Court failed to address the evidentiary issues including the base‐rate fallacy—a lethal defect. It also finds that neither the Member States nor the Commission have even tried to assess whether the operation of the PNR Directive has resulted in discriminatory outputs or outcomes; and that the Court should have demanded that they produce serious, verifiable data on this, including on whether the PNR system has led in practice to discrimination. But it also finds that the AG and the Court provided important guidance on the third issue, in that they made clear that the use of unexplainable and hence unreviewable and unchallengeable “black box” machine‐learning artificial intelligence (ML/AI) systems violates the very essence of the right to an effective remedy. This means that any EU Member State that still uses such opaque ML/AI systems in its PNR screening will be in violation of the law.
The role of an artificial intelligence model in antiretroviral therapy counselling and advice for people living with HIV
Authors: Koh Matthew Chung Yi , Ngiam Jinghao Nicholas , Yong Joy , Tambyah Paul Anantharajah , Archuleta Sophia
Published: January 2024

Objectives

People living with HIV may find personalized access to accurate information on antiretroviral therapy (ART) challenging given the stigma and costs potentially associated with attending physical consultations. Artificial intelligence (AI) chatbots such as ChatGPT may help to lower barriers to accessing information addressing concerns around ART initiation. However, the safety and accuracy of the information provided remains to be studied.

Methods

We instructed ChatGPT to answer questions that people living with HIV frequently ask about ART, covering i) knowledge of and access to ART; ii) ART initiation, side effects, and adherence, and iii) general sexual health practices while receiving ART. We checked the accuracy of the advice against international HIV clinical practice guidelines.

Results

ChatGPT answered all questions accurately and comprehensively. It recognized potentially life‐threatening scenarios such as abacavir hypersensitivity reaction and gave appropriate advice. However, in certain contexts, such as specific geographic locations or for pregnant individuals, the advice lacked specificity to an individual's unique circumstances and may be inadequate. Nevertheless, ChatGPT consistently re‐directed the individual to seek help from a healthcare professional to obtain targeted advice.

Conclusions

ChatGPT may act as a useful adjunct in the process of ART counselling for people living with HIV. Improving access to information on and knowledge about ART may improve access and adherence to ART and outcomes for people living with HIV overall.
Low‐temperature sintering Sm‐doped PMN–PZ–PT multilayer ceramic actuator with high strain and temperature stability
Authors: Guo Qinghu , Wang Pengbin , Meng Xiangyu , Li Dongxu , Yao Zhonghua , Sun Huajun , Hao Hua , Liu Hanxing , Zhang Shujun
Published: January 2024

Multilayer ceramic actuators find extensive utility in applications requiring precise displacement control or force output, due to their advantages of high precision control, rapid response, low driving voltage, low power consumption, and so on. For practical applications, there is a need for high‐performance multilayer ceramic actuators (MLAs) that combine cost‐effectiveness, efficiency, and temperature stability. In this work, 1.5 mol%Sm‐doped 0.25 Pb(Mg1/3Nb2/3)O3–0.36PbZrO3–0.39PbTiO3 piezoelectric ceramics with PbO–CuO as sintering aid were fabricated. The addition of PbO–CuO significantly reduced the sintering temperature by 300°C, while having minimal impact on the piezoelectric properties. The optimized sintering condition, achieved at a low sintering temperature of 950°C with the introduction of a tiny 0.4 wt% sintering aid, yields impressive piezoelectric strain coefficient d33* = 690 pm/V. This substantiates the viability of employing low‐cost Ag/Pd (90/10) as inner electrode, which can be co‐fired with ceramic layer to fabricate MLA. This innovation enables a remarkable displacement of 1 µm at a low driving voltage of 200 V across a 9‐layers piezoelectric actuator, accompanied by high‐temperature stability, exhibiting <20% variation over the temperature range of 30–250°C. These results underscore a great potential for high‐performance piezoelectric actuators over a broad temperature range.
When I say … technology
Authors: Nageswaran Priyanka
Published: January 2024

Highlighting one of the themes from 2024's State of the Science issue, Nageswaran offers insight into the term "Technology," arguing for the importance of balancing tech benefits with human‐centric skills.
Drought memory in Acanthostachys strobilacea, a CAM epiphytic bromeliad
Authors: Carvalho V. , Gaspar M. , Nievola C. C.
Published: January 2024

Stress memory is the development of altered responses to stress due to previous exposure, which might result in increased tolerance. Biochemical and physiological parameters shown to be positively affected by stress memory include those of the antioxidant and nitrosative metabolism, photosynthetic pigments and osmolyte content. Epiphytic bromeliads likely present stress memory since they experience frequent droughts in the canopies. Thus, we aimed to evaluate if the epiphytic bromeliad Acanthostachys strobilacea (Schult. & Schult.f.) Klotzsch shows improved metabolic stress defence responses to a second drought and rewatering cycle compared to a single exposure.

In a controlled environment chamber, 90‐day‐old plants were exposed to one or two drought–rewatering cycles of 14 days without irrigation and 5 days of rewatering each. Sampling occurred after the final drought and rewatering periods for one or two cycles treatments.

The free amino acid, chlorophyll, and carotenoid levels and S‐nitrosoglutathione reductase (GSNOR) activity were higher at the second drought than at the first exposure. The rise in nocturnal acidification (indicative of increased CAM activity) caused by the initial drought persisted through the second drought–rewatering cycle, implying a lasting memory effect on CAM activity. Furthermore, the second recovery did not induce glutathione accumulation, as in the first rewatering event, suggesting the pre‐exposure to drought reduced this thiol's demand during a later recovery.

Our results evidence metabolic changes related to drought stress memory in A. strobilacea, supporting this mechanism might be involved in the tolerance of epiphytic bromeliads to intermittent droughts.
Unraveling the Molecular Functions of Multifaced Plant‐Vacuolar Processing Enzymes
Authors: Sarwar Rehman , Yu Jiang , Zekraoui Meryem , Wang Yong , Zhu Ke‐ming , Tan Xiao‐Li
Published: January 2024

In the plant development cycle, different types of proteases play essential functions. Plant vacuolar processing enzymes (VPEs) are a group of cysteine proteases localized in the cell vacuoles that process and regulate several larger proprotein precursors. VPEs activate the proteolytic cleavage of proproteins precursors within aspartic acid and asparagine residues to trigger the tightly controlled programmed cell death process induced by different stages of plant development and environmental cues, impacting myriad plant physiological processes. In plants, VPEs are categorized into embryo, vegetative, and seed coat‐types, in which embryo and seed coat‐type VPEs are mainly involved in processing the seed storage protein precursors to provide nutrients for early growth, while the vegetative type induces programmed cell death in a varied range of vegetative tissues. Recently, several plant VPEs exhibited transpeptidase activity, which is essential for the cyclization mechanism during the production of cyclotides. In this review, we explore and understand the complex functions of plant VPEs, which can lead to the production of stress‐tolerant and higher‐yield crops, and provide the recent advances in the application of VPEs in molecular pharming, which highlights the significant implications of VPEs in protein science and agriculture.
Abscisic acid inhibits germination of Striga seeds and is released by them likely as a rhizospheric signal supporting host infestation
Authors: Jamil Muhammad , Alagoz Yagiz , Wang Jian You , Chen Guan‐Ting Erica , Berqdar Lamis , Kharbatia Najeh M. , Moreno Juan C. , Kuijer Hendrik N. J. , Al‐Babili Salim
Published: January 2024

Seeds of the root parasitic plant Striga hermonthica undergo a conditioning process under humid and warm environments before germinating in response to host‐released stimulants, particularly strigolactones (SLs). The plant hormone abscisic acid (ABA) regulates different growth and developmental processes, and stress response; however, its role during Striga seed germination and early interactions with host plants is under‐investigated. Here, we show that ABA inhibited Striga seed germination and that hindering its biosynthesis induced conditioning and germination in unconditioned seeds, which was significantly enhanced by treatment with the SL analog rac‐GR24. However, the inhibitory effect of ABA remarkably decreased during conditioning, confirming the loss of sensitivity towards ABA in later developmental stages. ABA measurement showed a substantial reduction of its content during the early conditioning stage and a significant increase upon rac‐GR24‐triggered germination. We observed this increase also in released seed exudates, which was further confirmed by using the Arabidopsis ABA‐reporter GUS marker line. Seed exudates of germinated seeds, containing elevated levels of ABA, impaired the germination of surrounding Striga seeds in vitro and promoted root growth of a rice host towards germinated Striga seeds. Application of ABA as a positive control caused similar effects, indicating its function in Striga/Striga and Striga/host communications. In summary, we show that ABA is an essential player during seed dormancy and germination processes in Striga and acts as a rhizospheric signal likely to support host infestation.
A point mutation in the meiotic crossover formation gene HEI10/TFS2 leads to thermosensitive genic sterility in rice
Authors: Zhang Zheng , Guo Yu‐Yi , Wang Yi‐Chen , Zhou Lei , Fan Jing , Mao Yi‐Chen , Yang Yan‐Ming , Zhang Yan‐Fei , Huang Xue‐Hui , Zhu Jun , Zhang Cheng , Yang Zhong‐Nan
Published: January 2024

Thermosensitive genic female sterility (TGFS) is a promising property to be utilized for hybrid breeding. Here, we identified a rice TGFS line, tfs2, through an ethyl methyl sulfone (EMS) mutagenesis strategy. This line showed sterility under high temperature and became fertile under low temperature. Few seeds were produced when the tfs2 stigma was pollinated, indicating that tfs2 is female sterile. Gene cloning and genetic complementation showed that a point mutation from leucine to phenylalanine in HEI10 (HEI10tfs2), a crossover formation protein, caused the TGFS trait of tfs2. Under high temperature, abnormal univalents were formed, and the chromosomes were unequally segregated during meiosis, similar to the reported meiotic defects in oshei10. Under low temperature, the number of univalents was largely reduced, and the chromosomes segregated equally, suggesting that crossover formation was restored in tfs2. Yeast two‐hybrid assays showed that HEI10 interacted with two putative protein degradation‐related proteins, RPT4 and SRFP1. Through transient expression in tobacco leaves, HEI10 were found to spontaneously aggregate into dot‐like foci in the nucleus under high temperature, but HEI10tfs2 failed to aggregate. In contrast, low temperature promoted HEI10tfs2 aggregation. This result suggests that protein aggregation at the crossover position contributes to the fertility restoration of tfs2 under low temperature. In addition, RPT4 and SRFP1 also aggregated into dot‐like foci, and these aggregations depend on the presence of HEI10. These findings reveal a novel mechanism of fertility restoration and facilitate further understanding of HEI10 in meiotic crossover formation.
Longitudinal pilot study examining the effect of punch biopsy on equine sarcoid growth dynamics
Authors: Gysens Lien , Martens Ann , Haspeslagh Maarten
Published: January 2024

Background

Nonexcisional tissue biopsies facilitate pre‐operative confirmation of equine sarcoid yet fear of lesion deterioration currently limits its use in the diagnostic workup.

Objectives

To evaluate the effect of a single punch biopsy on tumour growth dynamics [thickness, area, circumference, viral load (VL) and Visual Analog Scale (VAS)].

Animals

Six client‐owned horses with 11 sarcoids of various classification.

Materials and Methods

Growth dynamics were recorded on a weekly basis, 12 weeks pre‐ and 24 weeks post‐biopsy. The effect of a single punch biopsy on growth dynamics was estimated by linear mixed‐effect models. Spearman's rank correlation coefficient (SRCC) was calculated to investigate correlations with the number of weeks before and after the intervention.

Results

While statistically significant post‐biopsy changes were recorded for all parameters except VL, no parameter was consistently increased after the biopsy intervention. In two of 11 sarcoids, the VL correlation pattern revealed significant strong correlations: sarcoid 6 (pre: r = −0.66, p < 0.05; post: r = 0.81, p < 0.001), increased VL; and sarcoid 8 (pre: r = 0.85, p < 0.001; post: r = 0.17, p > 0.05), no further increase after biopsy.

Conclusions and Clinical Importance

Our results indicate that post‐biopsy lesion deterioration is not a general concept that applies to all sarcoids, and both deterioration or improvement are possible outcomes over a 24‐week period. Further clinical studies with a larger sample size are needed before a definitive conclusion can be made.
The Shih Tzu eye: Ophthalmic findings of 1000 eyes
Authors: Rajaei Seyed Mehdi , Faghihi Houman , Zahirinia Fatemeh
Published: January 2024

Purpose

To evaluate the frequency of ophthalmic disorders in Shih Tzus.

Animals

Five hundred client‐owned Shih Tzu dogs (1000 eyes).

Procedures

Medical records of 500 Shih Tzu dogs were reviewed and ophthalmic examination data were collected and analyzed.

Results

In total, out of 1000 eyes, 964 (96.4%; OD: 480 eyes, OS: 484 eyes) had at least one ophthalmic abnormality, and only 36 eyes (3.6%; OD: 20 eyes, OS: 16 eyes) were diagnosed as normal. A total of 1375 individual ophthalmic abnormalities were observed in 964 diseased eyes. Fifty‐nine different unique diagnoses were made in the study population, and only three conditions [medial canthal entropion (10.4% of eyes; bilateral in 10.2% of dogs), caruncular trichiasis (21.1% of eyes; bilateral in 20.2% of dogs), and reduced tear film breakup time (17.6% of eyes; bilateral in 17.4% of dogs)] affected 49.1% of the eyes.

Conclusion and Clinical Relevance

Findings suggested that the most prevalent disorders for the Shih Tzus were hairy caruncle, reduced TBUT, medial canthal entropion, keratoconjunctivitis sicca, pigmentary keratitis, lagophthalmos, and mature cataract.
Age-Related Constraints in the Visuomotor Plasticity of Postural Control as Revealed by a Whole-Body Mirror Learning Task
Authors: Christodoulou Iasonas , Mylonas Vasileios , Kannas Theodoros M. , Sotirakis Charalampos , Mademli Lida , Kouidi Evangelia , Hatzitaki Vassilia
Published: January 2024

Whether visuomotor plasticity of postural control is a trainable feature in older age remains an open question despite the wealth of visually guided exercise games promising to improve balance skill. We asked how aging affects adaptation and learning of a visual feedback (VF) reversal during visually guided weight shifting and whether this skill is modulated by explicit knowledge. Twenty-four older (71.43 ± 2.54 years) and 24 young (24.04 ± 0.93 years) participants were exposed to a 180° VF reversal while tracking a horizontally moving target by voluntarily weight shifting between two force platforms. An explicit strategy was available to half of the participants with detailed instruction to counter the VF rotation. Individual error data were fitted to an exponential function to assess adaptation. Fewer older (12/24) than younger (21/24) participants adapted to the VF reversal, displaying error curves that fitted the exponential function. Older adults who adapted to the VF reversal (responders, n = 12) reached an asymptote in performance in the same weight shifting cycle and displayed a similar mean asymptotic error compared with young participants. Young but not older responders exhibited an aftereffect when the VF reversal was removed. Instruction did not influence spatial error modulations regardless of age. The large individual variations within the older adults’ group during early adaptation suggest age-specific limitations in using explicit cognitive strategies when older adults are exposed to an abrupt mirror feedback reversal that requires a change in weight shifting direction during whole-body postural tracking.
Zinc-copper dual-ion electrolytes to suppress dendritic growth and increase anode utilization in zinc ion capacitors
Authors: Shin Chanho , Yao Lulu , Jeong Seong-Yong , Ng Tse Nga
Published: January 2024

The main bottlenecks that hinder the performance of rechargeable zinc electrochemical cells are their limited cycle lifetime and energy density. To overcome these limitations, this work studied the mechanism of a dual-ion Zn-Cu electrolyte to suppress dendritic formation and extend the device cycle life while concurrently enhancing the utilization ratio of zinc and thereby increasing the energy density of zinc ion capacitors (ZICs). The ZICs achieved a best-in-class energy density of 41 watt hour per kilogram with a negative-to-positive (n/p) electrode capacity ratio of 3.10. At the n/p ratio of 5.93, the device showed a remarkable cycle life of 22,000 full charge-discharge cycles, which was equivalent to 557 hours of discharge. The cumulative capacity reached ~581 ampere hour per gram, surpassing the benchmarks of lithium and sodium ion capacitors and highlighting the promise of the dual-ion electrolyte for delivering high-performance, low-maintenance electrochemical energy supplies.
Adaptive immune cells are necessary for SARS-CoV-2–induced pathology
Authors: Imbiakha Brian , Sahler Julie M. , Buchholz David W. , Ezzatpour Shahrzad , Jager Mason , Choi Annette , Monreal Isaac A. , Byun Haewon , Adeleke Richard Ayomide , Leach Justin , Whittaker Gary , Dewhurst Stephen , Rudd Brian D. , Aguilar Hector C. , August Avery
Published: January 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic associated with morbidity and mortality in humans. Although disease severity correlates with immune dysregulation, the cellular mechanisms of inflammation and pathogenesis of COVID-19 remain relatively poorly understood. Here, we used mouse-adapted SARS-CoV-2 strain MA10 to investigate the role of adaptive immune cells in disease. We found that while infected wild-type mice lost ~10% weight by 3 to 4 days postinfection,

rag
−/−

mice lacking B and T lymphocytes did not lose weight. Infected lungs at peak weight loss revealed lower pathology scores, fewer neutrophils, and lower interleukin-6 and tumor necrosis factor–α in

rag
−/−

mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into

rag
−/−

mice did not significantly change the response. Collectively, these findings suggest that while adaptive immune cells are important for clearing SARS-CoV-2 infection, this comes at the expense of increased inflammation and pathology.
An
in vitro
medium for modeling gut dysbiosis associated with cystic fibrosis
Authors: Barrack Kaitlyn E. , Hampton Thomas H. , Valls Rebecca A. , Surve Sarvesh V. , Gardner Timothy B. , Sanville Julie L. , Madan Juliette L. , O’Toole George A.
Published: January 2024

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation, and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization, and competition with other microbes. The impact of any specific change in this physiological landscape is difficult to parse using human or animal studies. Thus, we have developed a novel culture medium representative of the CF gut environment, inclusive of all the aforementioned features. This medium, called CF-MiPro, maintains CF gut microbiome communities, while significantly shifting nonCF gut microbiome communities toward a CF-like microbial profile, characterized by low Bacteroidetes and high Proteobacteria abundance. This medium is able to maintain this culture composition for up to 5 days of passage. Additionally, microbial communities passaged in CF-MiPro produce significantly less immunomodulatory short-chain fatty acids (SCFA), including propionate and butyrate, than communities passaged in MiPro, a culture medium representative of healthy gut physiology, confirming not only a shift in microbial composition but also altered community function. Our results support the potential for this
in vitro
culture medium as a new tool for the study of CF gut dysbiosis.

IMPORTANCE

Cystic fibrosis is an autosomal recessive disease that disrupts ion transport at mucosal surfaces, leading to mucus accumulation and altered physiology of both the lungs and the intestines, among other organs, with the resulting altered environment contributing to an imbalance of microbial communities. Culture media representative of the CF airway have been developed and validated; however, no such medium exists for modeling the CF intestine. Here, we develop and validate a first-generation culture medium inclusive of features that are altered in the CF colon. Our findings suggest this novel medium, called CF-MiPro, as a maintenance medium for CF gut microbiome samples and a flexible tool for studying key drivers of CF-associated gut dysbiosis.
Novel small-molecule compound YH7 inhibits the biofilm formation of
Staphylococcus aureus
in a
sarX
-dependent manner
Authors: Xiao Yanghua , Wan Cailing , Wu Xiaocui , Xu Yanlei , Chen Yao , Rao Lulin , Wang Bingjie , Shen Li , Han Weihua , Zhao Huilin , Shi Junhong , Zhang Jiao , Song Zengqiang , Yu Fangyou
Published: January 2024

The emergence of antibiotic-resistant and biofilm-producing
Staphylococcus aureus
isolates presents major challenges for treating staphylococcal infections. Biofilm inhibition is an important anti-virulence strategy. In this study, a novel maleimide-diselenide hybrid compound (YH7) was synthesized and demonstrated remarkable antimicrobial activity against methicillin-resistant
S. aureus
(MRSA) and methicillin-susceptible
S. aureus
(MSSA) in both planktonic cultures and biofilms. The minimum inhibitory concentration (MIC) of YH7 for
S. aureus
isolates was 16 µg/mL. Quantification of biofilms demonstrated that the sub-MIC (4 µg/mL) of YH7 significantly inhibits biofilm formation in both MSSA and MRSA. Confocal laser scanning microscopy analysis further confirmed the biofilm inhibitory potential of YH7. YH7 also significantly suppressed bacterial adherence to A549 cells. Moreover, YH7 treatment significantly inhibited
S. aureus
colonization in nasal tissue of mice. Preliminary mechanistic studies revealed that YH7 exerted potent biofilm-suppressing effects by inhibiting polysaccharide intercellular adhesin (PIA) synthesis, rather than suppressing bacterial autolysis. Real-time quantitative PCR data indicated that YH7 downregulated biofilm formation-related genes (
clfA
,
fnbA
,
icaA,
and
icaD
) and the global regulatory gene
sarX
, which promotes PIA synthesis. The
sarX
-dependent antibiofilm potential of YH7 was validated by constructing
S. aureus
NCTC8325
sarX
knockout and complementation strains. Importantly, YH7 demonstrated a low potential to induce drug resistance in
S. aureus
and exhibited non-toxic to rabbit erythrocytes, A549, and BEAS-2B cells at antibacterial concentrations.
In vivo
toxicity assays conducted on
Galleria mellonella
further confirmed that YH7 is biocompatible. Overall, YH7 demonstrated potent antibiofilm activity supports its potential as an antimicrobial agent against
S. aureus
biofilm-related infections.

IMPORTANCE

Biofilm-associated infections, characterized by antibiotic resistance and persistence, present a formidable challenge in healthcare. Traditional antibacterial agents prove inadequate against biofilms. In this study, the novel compound YH7 demonstrates potent antibiofilm properties by impeding the adhesion and the polysaccharide intercellular adhesin production of
Staphylococcus aureus
. Notably, its exceptional efficacy against both methicillin-resistant and methicillin-susceptible strains highlights its broad applicability. This study highlights the potential of YH7 as a novel therapeutic agent to address the pressing issue of biofilm-driven infections.
Toroidal flow around the Tonga slab moved the Samoan plume during the Pliocene
Authors: Konrad Kevin , Jackson Matthew , Steinberger Bernhard , Koppers Anthony , Balbas Andrea , Finlayson Valerie , Konter Jasper , Price Allison
Published: January 2024

Age-progressive seamount tracks generated by lithospheric motion over a stationary mantle plume have long been used to reconstruct absolute plate motion (APM) models. However, the basis of these models requires the plumes to move significantly slower than the overriding lithosphere. When a plume interacts with a convergent or divergent plate boundary, it is often deflected within the strong local mantle flow fields associated with such regimes. Here, we examined the age progression and geometry of the Samoa hotspot track, focusing on lava flow samples dredged from the deep flanks of seamounts in order to best reconstruct when a given seamount was overlying the mantle plume (i.e., during the shield-building stage). The Samoan seamounts display an apparent local plate velocity of 7.8 cm/yr from 0 to 9 Ma, 11.1 cm/yr from 9 to 14 Ma, and 5.6 cm/yr from 14 to 24 Ma. Current fixed and mobile hotspot Pacific APM models cannot reproduce the geometry of the Samoa seamount track if a long-term fixed hotspot location, currently beneath the active Vailulu’u Seamount, is assumed. Rather, reconstruction of the eruptive locations of the Samoan seamounts using APM models indicates that the surface expression of the plume migrated ~2° northward in the Pliocene. Large-scale mantle flow beneath the Pacific Ocean Basin cannot explain this plume migration. Instead, the best explanation is that toroidal flow fields—generated by westward migration of the Tonga Trench and associated slab rollback—have deflected the conduit northward over the past 2–3 m.y. These observations provide novel constraints on the ways in which plume-trench interactions can alter hotspot track geometries.
The utility of heart rate and heart rate variability to identify limits of tolerance to moderate-intensity work in the heat: a secondary analysis
Authors: De Barros Jordan A. , Macartney Michael J. , Notley Sean R. , Meade Robert D. , Kenny Glen P.
Published: January 2024

We investigated the utility of heart rate (HR) and heart rate variability (HRV) for identifying individuals who may terminate work early due to excessive heat strain. Forty-eight men and women (median = 36 years; Q1 = 20 years; Q3 = 54 years) attempted 180 min of moderate-intensity work at a fixed metabolic rate (∼200 W/m2; ∼3.5 METs) in a hot environment (wet-bulb globe temperature: 32 °C). Receiver operating characteristics (ROC) curves were used to identify the ability of indices of HR (absolute HR, percentage of maximum HR, percentage of HR reserve) and HRV (root-mean-square of successive differences (RMSSD), high-frequency power, and detrended fluctuation analysis component alpha 1 (DFA α1)) to discriminate between participants who completed the 180 min work bout or terminated prematurely. Participants who terminated work prematurely ( n = 26) exhibited higher HR and percentage of HR measures, as well as reduced RMSSD and DFA α1 after the first hour of work compared to participants who completed the bout. The discriminative utility of HR and HRV indices was strongest within the first hour of work, with percentage of HR reserve demonstrating excellent discriminative power (ROC area under curve (AUC) of 0.8). Stratifying participants by age and sex improved ROC AUC point estimates for most indices, particularly in female participants. The study provides preliminary evidence supporting the use of noninvasive cardiac monitoring for predicting work tolerance in healthy individuals exposed to occupational heat stress. HR and percentage of HR reserve were suggested to discriminate work termination most effectively. Further investigations are warranted to explore the influence of individual factors and refine the discriminative thresholds for early identification of excessive occupational heat strain.
Kernel Probabilistic Dependent-Independent Canonical Correlation Analysis
Authors: Rohani Sarvestani Reza , Gholami Ali , Boostani Reza
Published: January 2024

There is growing interest in developing linear/nonlinear feature fusion methods that fuse the elicited features from two different sources of information for achieving a higher recognition rate. In this regard, canonical correlation analysis (CCA), cross-modal factor analysis, and probabilistic CCA (PCCA) have been introduced to better deal with data variability and uncertainty. In our previous research, we formerly developed the kernel version of PCCA (KPCCA) to capture both nonlinear and probabilistic relation between the features of two different source signals. However, KPCCA is only able to estimate latent variables, which are statistically correlated between the features of two independent modalities. To overcome this drawback, we propose a kernel version of the probabilistic dependent-independent CCA (PDICCA) method to capture the nonlinear relation between both dependent and independent latent variables. We have compared the proposed method to PDICCA, CCA, KCCA, cross-modal factor analysis (CFA), and kernel CFA methods over the eNTERFACE and RML datasets for audio-visual emotion recognition and the M2VTS dataset for audio-visual speech recognition. Empirical results on the three datasets indicate the superiority of both the PDICCA and Kernel PDICCA methods to their counterparts.
Study on the Optimal Phospholipid Addition Levels for Button‐Sized Juvenile Chinese Mitten Crab (Eriocheir sinensis): Survival, Growth, Physiological Parameters, and Neverland Expression
Authors: Zuo Rantao , Yuan Rong , Shi Weishuai , Tao Changhong , Yi Qilin , Huang Shu , Su Yanming , Jiang Yusheng
Published: January 2024

A 50‐day feeding experiment was performed to investigate the effects of dietary phospholipid (PL) addition on the survival, growth, serum, and hepatopancreas lipid indexes, calcium content, and neverland (Nvd) gene expression in button‐sized juvenile Chinese mitten crab (Eriocheir sinensis). Five experimental diets were formulated with increasing addition of PL (0%, 1%, 2%, 3%, and 4%), which were named PL0, PL1, PL2, PL3, and PL4, respectively. Each diet was randomly assigned to four tanks of juvenile E. sinensis (initial weight: 5.00 ± 0.55 g), with eight crabs held in each tank. The results showed that PL addition significantly increased the survival rate (SR) but just slightly increased the weight gain rate (WGR) of juvenile E. sinensis. As the PL addition level increased, SR and WGR first increased and then decreased, with the highest values observed in the PL3 group. As the PL addition level increased, the activities of trypsin and cellulase significantly increased and then decreased, with the highest value observed in the PL2 group and PL3 group, respectively. As PL addition level increased from 1% to 2%, lipase activity increased sharply and then kept constant with a further increase of dietary PL. As PL addition level increased from 0% to 3%, the calcium content in the serum significantly increased from 7.96 to 12.43 mmol/L and then significantly decreased to 11.36 mmol/L with a further increase of PL addition. PL addition just slightly promoted the calcium content in the hepatopancreas compared with the control group. As PL addition level increased from 0% to 3%, the expression of Nvd in the hepatopancreas significantly increased by 1.47‐fold and then decreased to basal level with a further increase of PL addition. In conclusion, 2%−3% addition of the optimal PL addition level was estimated to be 2%−3% for juvenile E. sinensis based on their survival, growth performance, and digestive enzyme activities. PL addition at a relatively higher level (3%) increased the calcium content and Nvd expression, the latter possibly facilitating cholesterol metabolism into vitamin D.
Tumor-Associated Macrophages in Merkel Cell Carcinoma: Old Balances, New Checks
Authors: Silk Ann W. , Davar Diwakar
Published: January 2024

A recent report sheds light on the tumor-associated macrophages (TAM) in Merkel cell carcinoma (MCC), and the association of S100A8-expressing TAMs with resistance to anti–PD-(L)1 inhibitors. These data improve our understanding about why some tumors with brisk tumor-infiltrating lymphocytes do not respond to immunotherapy and provide a compelling rationale to target myeloid checkpoints in MCC.

See related article by Tabachnick-Cherny et al., p. 1189
Supplementary Table 7 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 7
Supplementary Table 5 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 5
Figure S5 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity
Authors: Heiser Ryan A. , Cao Anthony T. , Zeng Weiping , Ulrich Michelle , Younan Patrick , Anderson Martha E. , Trueblood Esther S. , Jonas Mechthild , Thurman Robert , Law Che-Leung , Gardai Shyra J.
Published: January 2024

Supplementary Figure S5. Brentuximab vedotin enhances cytotoxic T-cell infiltration into LCL tumors
Figure S3 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity
Authors: Heiser Ryan A. , Cao Anthony T. , Zeng Weiping , Ulrich Michelle , Younan Patrick , Anderson Martha E. , Trueblood Esther S. , Jonas Mechthild , Thurman Robert , Law Che-Leung , Gardai Shyra J.
Published: January 2024

Supplementary Figure S3. Raw pixel intensities for western blots in Figure 2
Supplementary Table S1 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

qRT-PCR primers used in this study.
Supplementary Figure S5 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

The shortened aCx26-pep 216-220 attenuates tumorsphere-formation frequency similarly to the full-length aCx26-pep only in TNBC. *** p<0.001 by Chi-squared test compared to aScr-pep. Shown is one replicate representative of three independent experiments.
Supplementary Figure S1 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

Predicted model of Cx26 in complex with NANOG and FAK.
Supplemental Figure 3 from Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling
Authors: Li Wei , Sano Renata , Apatira Mutiah , DeAnda Felix , Gururaja Tarikere , Yang Muhua , Lundgaard Greta , Pan Chin , Liu Jing , Zhai Yongjiao , Yoon Woo Hyun , Wang Longcheng , Tse Chris , Souers Andrew J. , Lee Chih-Hung
Published: January 2024

Supplemental Figure 3
Supplemental Figure 1 from Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling
Authors: Li Wei , Sano Renata , Apatira Mutiah , DeAnda Felix , Gururaja Tarikere , Yang Muhua , Lundgaard Greta , Pan Chin , Liu Jing , Zhai Yongjiao , Yoon Woo Hyun , Wang Longcheng , Tse Chris , Souers Andrew J. , Lee Chih-Hung
Published: January 2024

Supplemental Figure 1
Supplementary Table S9 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Whole exome sequencing results for CUTO37-ER vs CUTO37 and H3122-CR vs H3122.
Supplementary Table S7 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

STRING protein-protein interaction confidence scores for EGFR and the other 26 genes identified in the enriched GO term "regulation of ERBB signaling pathway" in CUTO28 crizotinib vs DMSO pY phosphoproteomics.
Table S2 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Systemic and CNS exposure of BI-907828 in FVB triple-knockout and BCRP-knockout mice after a single intravenous bolus dose of 10 mg/kg
Supplementary Table S3 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

The complete list of identified phosphopeptides after pY enrichment in crizotinib vs DMSO treated H3122 cells with fold changes and p-value calculation.
Supplementary Table S13 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Patient cases of concurrent alterations with ERRFI1 deep-deletion or EBD truncation mutations.
Figure S4 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Expression of p53 and target genes in GBM120 and GBM108 evaluated by Western blot at 6 hours after BI-907828 treatment.
Table S3 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Table S3 contains response numbers for in vivo efficacy study
Table S2 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Table S2 supplies IC50 values for ADCs over a range of in vitro cytotox assays
Table S1 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Table S1 contains measured DARs for ADCs used
Figure S3 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Figure S3 shows body weights of animals at two doses
Figure S2 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Figure S2 shows a graphical representation of IC50 spread over range of cytotoxicity experiments
Table S4 from Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy
Authors: Pham Andrew C. , Holstein Sarah A. , Borgstahl Gloria E.O.
Published: January 2024

List of drug-bound PDB structures
Supplementary Methods from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

X-ray specifications
Table S3 from Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy
Authors: Pham Andrew C. , Holstein Sarah A. , Borgstahl Gloria E.O.
Published: January 2024

Residues involved in GGDP binding
Figure S3 from Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy
Authors: Pham Andrew C. , Holstein Sarah A. , Borgstahl Gloria E.O.
Published: January 2024

The electrostatic surface of the hGGDPSAF enzyme A. without magnesium in the active site and B. with magnesium in the active site. Magnesium ions contribute positive charge across the protein allowing for stable binding with the phosphate heads of the substrate and product. Areas outlined in the yellow dotted approximate the surfaces located closest to the active site. The magnesium ions may also play roles in drawing in the negatively charged substrate. Figure generated with the APS electrostatics tool in PyMOL.
Figure S1 from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

Figure S1 shows A) Fraction of transfected cells after re-expression of NF2 in HEK293 and NF2-mutant mesothelioma cell lines. The proliferation of NF2-mutant mesothelioma cell lines, but not the NF2 wild-type HEK293 cells, is suppressed by NF2 overexpression. B) Effect of SWTX-143 on the proliferation of the Hippo-wild type mesothelioma cell line H2062.